inhibitor of heme oxidation. *Proceedings of the National Academy of Sciences of the United States of America*, **78**, 6466–6470.

134. Kachadourian, R., Biochev, S. I., Cabelli, D. E., Patel, M. N., Fridovich, I., & Day, B. J. (2001). 2-Methoxyestradiol does not inhibit superoxide dismutase. *Archives of Biochemistry and Biophysics*, **392**, 349–353.

135. Griffith, O. W. (1982). Mechanism of action, metabolism, and toxicity of buthionine sulfoximine and its higher homologs, potent inhibitors of glutathione synthesis. *Journal of Biological Chemistry*, **257**, 13704–13712.

136. Ueda, M., Kinoshita, H., Yoshida, T., Kamasawa, N., Osumi, M., & Tanaka, A. (2003). Effect of catalase-specific inhibitor 3-amino-1,2,4-triazole on yeast peroxisomal catalase in vivo. *FEMS Microbiology Letters*, **219**, 93–98.

137. García-Piñeres, A. J., Castro, V., Mora, G., Schmidt, T. J., Strunck, E., Pahl, H. L., & Merfort, I. (2001). Cysteine 38 in p65/NF-kappaB plays a crucial role in DNA binding inhibition by sesquiterpene lactones. *Journal of Biological Chemistry*, **276**, 39713–39720.

138. Erkel, G., Anke, T., & Sterner, O. (1996). Inhibition of NF-κB activation by panepoxydone. *Biochemical and Biophysical Research Communications*, **226**, 214–221.

139. Lee, J., Rhee, M. H., Kim, E., & Cho, J. Y. (2012). BAY 11-7082 is a broad-spectrum inhibitor with anti-inflammatory activity against multiple targets. *Mediators of Inflammation*, **2012**, 11.

140. Nishimura, D., Ishikawa, H., Matsumoto, K., Shibata, H., Motoyoshi, Y., Fukuta, M., Kawashimo, H., Goto, T., Taura, N., Ichikawa, T., Hamasaki, K., Nakao, K., Umezawa, K., & Eguchi, K. (2006). DHMEQ, a novel NF-κB inhibitor, induces apoptosis and cell-cycle arrest in human hepatoma cells. *International Journal of Oncology*, **29**, 713–719.

141. MacKenzie, E. D., Selak, M. A., Tennant, D. A., Payne, L. J., Crosby, S., Frederiksen, C. M., Watson, D. G., & Gottlieb, E. (2007). Cell-permeating α-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. *Molecular and Cellular Biology*, **27**, 3282–3289.

142. Hawkey, C. J. (1999). COX-2 inhibitors. *Lancet*, **353**, 307–314.

143. Song, H., Wang, R., Wang, S., & Lin, J. (2005). A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells. *Proceedings of the National Academy of Sciences of the United States of America*, **102**, 4700–4705.

144. Iwamaru, A., Szymanski, S., Iwado, E., Aoki, H., Yokoyama, T., Fokt, I., Hess, K., Conrad, C., Madden, T., Sawaya, R., Kondo, S., Priebe, W., & Kondo, Y. (2007). A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both in vitro and in vivo. *Oncogene*, **26**, 2435–2444.

145. Altieri, D. C. (2008). Survivin, cancer networks and pathway-directed drug discovery. *Nature Reviews Cancer*, **8**, 61–70.

146. Rose-John, S., Waetzig, G. H., Scheller, J., Grötzinger, J., & Seegert, D. (2007). The IL-6/sIL-6R complex as a novel target for therapeutic approaches. *Expert Opinion on Therapeutic Targets*, **11**, 613–624.

147. Brown, P. (1997). Matrix metalloproteinase inhibitors in the treatment of cancer. *Medical Oncology*, **14**, 1–10.

148. Yeo, E. J., Ryu, J. H., Cho, Y. S., Chun, Y. S., Huang, L. E., Kim, M. S., & Park, J. W. (2006). Amphotericin B blunts erythropoietin response to hypoxia by reinforcing FIH-mediated repression of HIF-1. *Blood*, **107**, 916–923.

149. Kong, D., Park, E. J., Stephen, A. G., Calvani, M., Cardellina, J. H., Monks, A., Fisher, R. J., Shoemaker, R. H., & Melillo, G. (2005). Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. *Cancer Research*, **65**, 9047–9055.

150. Choi, H., Chun, Y. S., Kim, S. W., Kim, M. S., & Park, J. W. (2006). Curcumin inhibits hypoxia-inducible factor-1 by

degrading aryl hydrocarbon receptor nuclear translocator: a mechanism of tumor growth inhibition. *Molecular Pharmacology*, **70**, 1664–1671.

151. Lee, K., Zhang, H., Qian, D. Z., Rey, S., Liu, J. O., & Semenza, G. L. (2009). Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. *Proceedings of the National Academy of Sciences of the United States of America*, **106**, 17910–17915.

152. Huang, C., Ma, W. Y., Dawson, M. I., Rincon, M., Flavell, R. A., & Dong, Z. (1997). Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic-acid. *Proceedings of National Academy of Sciences USA*, **94**, 5826–5830.

153. Bennett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sakata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., Bhagwat, S. S., Manning, A. M., & Anderson, D. W. (2001). SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. *Proceedings of the National Academy of Sciences of the United States of America*, **98**, 13681–13686.

154. Gallagher, T. F., Seibel, G. L., Kassis, S., Laydon, J. T., Blumenthal, M. J., Lee, J. C., Lee, D., Boehm, J. C., Fier-Thompson, S. M., Abt, J. W., Soreson, M. E., Smietana, J. M., Hall, R. F., Garigipati, R. S., Bender, P. E., Erhard, K. F., Krog, A. J., Hofmann, G. A., Sheldrake, P. L., McDonnell, P. C., Kumar, S., Young, P. R., & Adams, J. L. (1997). Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase. *Bioorganic and Medicinal Chemistry*, **5**, 49–64.

155. Hadden, K. M., Lubbers, D. J., & Blagg, B. S. J. (2006). Geldanamycin, radicicol, and chimeric inhibitors of the Hsp90 N-terminal ATP binding site. *Current Topics in Medicinal Chemistry*, **6**, 1173–1182.

156. Lundgren, K., Zhang, H., Brekken, J., Huser, N., Powell, R. E., Timple, N., Busch, D. J., Neely, L., Sensintaffar, J. L., Yang, Y.-c., McKenzie, A., Friedman, J., Scannevin, R., Kamal, A., Hong, K., Kasibhatla, S. R., Boehm, M. F., & Burrows, F. J. (2009). BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. *Molecular Cancer Therapeutics*, **8**, 921–929.

157. Lee, K.-H., Lee, J.-H., Han, S.-W., Im, S.-A., Kim, T.-Y., Oh, D.-Y., & Bang, Y.-J. (2011). Antitumor activity of NVP-AUY922, a novel heat shock protein 90 inhibitor, in human gastric cancer cells is mediated through proteasomal degradation of client proteins. *Cancer Science*, **102**, 1388–1395.

158. Chandarlapaty, S., Sawai, A., Ye, Q., Scott, A., Silinski, M., Huang, K., Fadden, P., Pardrige, J., Hall, S., Steed, P., Norton, L., Rosen, N., & Solit, D. B. (2008). SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. *Clinical Cancer Research*, **14**, 240–248.

159. Wang, Y., Trepel, J. B., Neckers, L. M., & Giaccone, G. (2010). STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer. *Current Opinion in Investigational Drugs*, **11**, 1466–1476.

160. Backer, J., Krivoshein, A. V., Hamby, C. V., Pizzonia, J., GK, S., Ray, Y. S., Brand, H., Paton, A. W., Paton, J. C., & Backer, M. V. (2009). Chaperone-targeting cytotoxin and endoplasmic reticulum stress-inducing drug synergize to kill cancer cells. *Neoplasia*, **11**, 1165–1173.

161. Schlecht, R., Scholz, S. R., Dahmen, H., Wegener, A., Sirrenberg, C., Musil, D., Bomke, J., Eggenweiler, H.-M., Mayer, M. P., & Bukau, B. (2013). Functional analysis of Hsp70 inhibitors. *PLoS ONE*, **8**, e78443.

162. Bonvini, P., Zorzi, E., Basso, G., & Rosolen, A. (2007). Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma. *Leukemia*, **21**, 838–842.
163. Zhang, H., Nakajima, S., Kato, H., Gu, L., Yoshitomi, T., Nagai, K., Shinmori, H., Kokubo, S., & Kitamura, M. (2013). Selective, potent blockade of the IRE1 and ATF6 pathways by 4-phenylbutyric acid analogues. *British Journal of Pharmacology*, **170**, 822–834.

164. Atkins, C., Liu, Q., Minthorn, E., Zhang, S.-Y., Figueroa, D. J., Moss, K., Stanley, T. B., Sanders, B., Goetz, A., Gaul, N., Choudhry, A. E., Alsaid, H., Jucker, B. M., Axten, J. M., & Kumar, R. (2013). Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. *Cancer Research*, **73**, 1993–2002.

165. Maines, M. D. (1981). Zinc-protoporphyrin is a selective inhibitor of heme oxygenase activity in the neonatal rat. *Biochimica et Biophysica Acta*, **673**, 339–350.

166. Kimani, S. G., Phillips, J. B., Bruce, J. I., MacRobert, A. J., & Golding, J. P. (2012). Antioxidant inhibitors potentiate the cytotoxicity of photodynamic therapy. *Photochemistry and Photobiology*, **88**, 175–187.

167. Misra, H. P. (1979). Reaction of copper-zinc superoxide dismutase with diethyldithiocarbamate. *Journal of Biological Chemistry*, **254**, 11623–11628.

168. Taylor, C. T., & Cummins, E. P. (2009). The role of NF-kappa B in hypoxia-induced gene expression. *Annals of the New York Academy of Sciences*, **1177**, 178–184.

169. Matroule, J.-Y., Volanti, C., & Piette, J. (2006). NF-κB in photodynamic therapy: discrepancies of a master regulator. *Photochemistry and Photobiology*, **82**, 1241–1246.

170. Song, J., Wei, Y., Chen, Q., & Xing, D. (2014). Cyclooxygenase 2-mediated apoptotic and inflammatory responses in photodynamic-ic therapy treated breast adenocarcinoma cells and xenografts. *Journal of Photochemistry and Photobiology B*, **134**, 27–36.

171. Ghosh, S., May, M. J., & Kopp, E. B. (2003). NF-κB and REL proteins: evolutionarily conserved mediators of immune responses. *Annual Review on Immunology*, **16**, 225–260.

172. Karin, M., Cao, Y., Greten, F. R., & Li, Z.-W. (2002). NF-kappaB in cancer: from innocent bystander to major culprit. *Nature Reviews Cancer*, **2**, 301–310.

173. Gloire, G., Charlier, E., Rahmouni, S., Volanti, C., Chariot, A., Erneux, C., & Piette, J. (2006). Restoration of SHIP-1 activity in human leukemic cells modifies NF-kappaB activation pathway and cellular survival upon oxidative stress. *Oncogene*, **25**, 5485–5494.

174. Storz, P., Döppler, H., & Toker, A. (2004). Protein kinase Cδ selectively regulates protein kinase D-dependent activation of NF-κB in oxidative stress signaling. *Molecular and Cellular Biology*, **24**, 2614–2626.

175. Storz, P., & Toker, A. (2003). Protein kinase D mediates a stress-induced NF-kappaB activation and survival pathway. *EMBO Journal*, **22**, 109–120.

176. Fan, C., Li, Q., Ross, D., & Engelhardt, J. F. (2003). Tyrosine phosphorylation of IκBα activates NFκB through a redox-regulated and c-Src-dependent mechanism following hypoxia/re-oxygenation. *Journal of Biological Chemistry*, **278**, 2072–2080.

177. Zhao, Q., & Lee, F. S. (1999). Mitogen-activated protein kinase/ERK kinase kinases 2 and 3 activate nuclear factor-κB through IκB kinase-α and IκB kinase-β. *Journal of Biological Chemistry*, **274**, 8355–8358.

178. Li, Q., & Engelhardt, J. F. (2006). Interleukin-1β induction of NFκB is partially regulated by H₂O₂-mediated activation of NFκB-inducing kinase. *Journal of Biological Chemistry*, **281**, 1495–1505.

179. Herscovitch, M., Comb, W., Ennis, T., Coleman, K., Yong, S., Armstead, B., Kalaitzidis, D., Chandani, S., & Gilmore, T. D. (2008). Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347. *Biochemical and Biophysical Research Communications*, **367**, 103–108.

180. Nakajima, S., & Kitamura, M. (2013). Bidirectional regulation of NF-κB by reactive oxygen species: a role of unfolded protein response. *Free Radical Biological Medicine*, **65**, 162–174.

181. Scholz, C. C., & Taylor, C. T. (2013). Hydroxylase-dependent regulation of the NF-κB pathway. *Biological Chemistry*, **394**, 479.

182. Cummins, E. P., Berra, E., Comerford, K. M., Ginouves, A., Fitzgerald, K. T., Seeballuck, F., Godson, C., Nielsen, J. E., Moynagh, P., Pouyssegur, J., & Taylor, C. T. (2006). Prolyl hydroxylase-1 negatively regulates IκB kinase-β, giving insight into hypoxia-induced NFκB activity. *Proceedings of National Academy of Sciences U S A*, **103**, 18154–18159.

183. Cummins, E. P., Comerford, K. M., Scholz, C., Bruning, U., Taylor, C. T., Helmut, S., & Bernhard, B. (2007). Hypoxic regulation of NF-kappaB signaling. *Methods in Enzymology*, **435**, 479–492.

184. Chu, W. M. (2012). Tumor necrosis factor. *Cancer Letters*, **328**, 222–225.

185. Han, D., Ybanez, M. D., Ahmadi, S., Yeh, K., & K, N. (2009). Redox regulation of tumor necrosis factor signaling. *Antioxidants and Redox Signaling*, **11**, 2245–2263.

186. Klatt, P., & Lamas, S. (2000). Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. *European Journal of Biochemistry*, **267**, 4928–4944.

187. Nishi, T., Shimizu, N., Hiramoto, M., Sato, I., Yamaguchi, Y., Hasegawa, M., Aizawa, S., Tanaka, H., Kataoka, K., Watanabe, H., & Handa, H. (2002). Spatial redox regulation of a critical cysteine residue of NF-κB in vivo. *Journal of Biological Chemistry*, **277**, 44548–44556.

188. Korn, S. H., Wouters, E. F. M., Vos, N., & Janssen-Heininger, Y. M. W. (2001). Cytokine-induced activation of nuclear factor-κB is inhibited by hydrogen peroxide through oxidative inactivation of IκB kinase. *Journal of Biological Chemistry*, **276**, 35693–35700.

189. Sakon, S., Xue, X., Takekawa, M., Sasazuki, T., Okazaki, T., Kojima, Y., Piao, J. H., Yagita, H., Okumura, K., Doi, T., & Nakano, H. (2003). NF-κB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. *EMBO Journal*, **22**, 3898–3909.

190. Heger, M., Beek, J. F., Moldovan, N. I., van der Horst, C. M. A. M., & van Gemert, M. J. C. (2005). Towards optimization of selective photothermolysis: prothrombotic pharmaceutical agents as potential adjuvants in laser treatment of port wine stains. A theoretical study. *Thrombosis and Haemostasis*, **93**, 242–256.

191. Guttridge, D. C., Albanese, C., Reuther, J. Y., Pestell, R. G., & Baldwin, A. S., Jr. (1999). NF-kappa B controls cell growth and differentiation through transcriptional regulation of cyclin D1. *Molecular and Cellular Biology*, **19**, 5785–5799.

192. Hayden, M. S., & Ghosh, S. (2008). Shared principles in NF-κB signaling. *Cell*, **132**, 344–362.

193. Hinz, M., Krappmann, D., Eichten, A., Heder, A., Scheidereit, C., & Strauss, M. (1999). NF-kappa B function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition. *Molecular and Cellular Biology*, **19**, 2690–2698.

194. Buytaert, E., Dewaele, M., & Agostinis, P. (2007). Molecular effectors of multiple cell death pathways initiated by photodynamic therapy. *Biochimica et Biophysica Acta*, **1776**, 86–107.

195. Volanti, C., Gloire, G., Vanderplasschen, A., Jacobs, N., Habraken, Y., & Piette, J. (2004). Downregulation of ICAM-1 and VCAM-1 expression in endothelial cells treated by photodynamic therapy. *Oncogene*, **23**, 8649–8658.

196. Karin, M., & Lin, A. (2002). NF-kappa B at the crossroads of life and death. *Nature Immunology*, **3**, 221–227.

197. van Uden, P., Kenneth, N. S., & Rocha, S. (2008). Regulation of hypoxia-inducible factor-1α by NF-κB. *Biochemistry Journal*, **412**, 477–484.
198. Hymowitz, S. G., & Wertz, I. E. (2010). A20: from ubiquitin editing to tumour suppression. *Nature Reviews Cancer, 10*, 332–341.

199. Castano, A. P., Mroz, P., & Hamblin, M. R. (2006). Photodynamic therapy and anti-tumour immunity. *Nature Reviews Cancer, 6*, 535–545.

200. de Groot, D. J. A., de Vries, E. G. E., Groen, H. J. M., & de Jong, S. (2007). Non-steroidal anti-inflammatory drugs to potentiate chemotherapy effects: from lab to clinic. *Critical Reviews in Oncology/Hematology, 61*, 52–69.

201. Kaidi, A., Qualtrough, D., Williams, A. C., & Paraskeva, C. (2006). Direct transcriptional up-regulation of cyclooxygenase-2 by hypoxia-inducible factor (HIF)-1 promotes colorectal tumor cell survival and enhances HIF-1 transcriptional activity during hypoxia. *Cancer Research, 66*, 6683–6691.

202. Luna, M., Wong, S., Ferrario, A., & Gomer, C. J. (2008). Cyclooxygenase-2 expression induced by photofrin photodynamic therapy involves the p38 MAPK pathway. *Photochemistry and Photobiology, 84*, 509–514.

203. Tanabe, T., & Tohnai, N. (2002). Cyclooxygenase isozymes and their gene structures and expression. *Prostaglandins Other Lipid Medicine, 68–69*, 95–114.

204. Wang, D., & DuBois, R. N. (2010). Eicosanoids and cancer. *Nature Reviews Cancer, 10*, 181–193.

205. Buchanan, F. G., Gorden, D. L., Matta, P., Shi, Q., Matrisian, L. M., & DuBois, R. N. (2006). Role of β-arrestin 1 in the metastatic progression of colorectal cancer. *Proceedings of the National Academy of Sciences of the United States of America, 103*, 1492–1497.

206. Buchanan, F. G., Wang, D., Bargiacchi, F., & DuBois, R. N. (2003). Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. *Journal of Biological Chemistry, 278*, 35451–35457.

207. Wang, D. & DuBois, R.N. (2010) Eicosanoids and cancer. *National Review Cancer* 10:181–193.

208. Han, C., Michalopoulos, G. K., & Wu, T. (2006). Prostaglandin E2 receptor EP1 transactivates EGFR/MET receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells. *Journal of Cellular Physiology, 207*, 261–270.

209. Ito, H., Duxbury, M., Benoit, E., Clancy, T. E., Zinner, M. J., Ashley, S. W., & Whang, E. E. (2004). Prostaglandin E2 enhances pancreatic cancer invasiveness through an Ets-1-dependent induction of matrix metalloproteinase-2. *Cancer Research, 64*, 7439–7446.

210. Pan, M. R., Hou, M. F., Chang, H. C., & Hung, W. C. (2008). Cyclooxygenase-2 up-regulates CCR7 via EP2/EP4 receptor signaling pathways to enhance lymphatic invasion of breast cancer cells. *Journal of Biological Chemistry, 283*, 11155–11163.

211. Abdel-Majid, R. M., & Marshall, J. S. (2004). Prostaglandin E2 induces degranulation-independent production of vascular endothelial growth factor by human mast cells. *Journal of Immunology, 172*, 1227–1236.

212. Dormond, O., Bezzi, M., Mariotti, A., & RÃ¹/egg, C. (2002). Prostaglandin E2 promotes integrin αVβ3-dependent endothelial cell adhesion, Rac-activation, and spreading through cAMP/PKA-dependent signaling. *Journal of Biological Chemistry, 277*, 45838–45846.

213. Salcedo, R., Zhang, X., Young, H. A., Michael, N., Wasserman, K., Ma, W.-H., Martins-Green, M., Murphy, W. J., & Oppenheim, J. J. (2003). Angiogenic effects of prostaglandin E2 are mediated by up-regulation of CXCR4 on human microvascular endothelial cells. *Blood, 102*, 1966–1977.

214. Cheung, C. H., Huang, C. C., Tsai, F. Y., Lee, J. Y., Cheng, S. M., Chang, Y. C., Huang, Y. C., Chen, S. H., & JY, C. (2013). Survivin—biology and potential as a therapeutic target in oncology. *Oncology Targets Thermometer, 6*, 1453–1462.

215. Boidot, R., Végran, F., & Lizard-Nacol, S. (2014). Transcriptional regulation of the survivin gene. *Molecular Biology Reports, 41*, 233–240.

216. Marusawa, H., Matsuzawa, S., Welsh, K., Zou, H., Armstrong, R., Tamm, I., & Reed, J. C. (2003). HBXIP functions as a cofactor of survivin in apoptosis suppression. *EMBO Journal, 22*, 2729–2740.

217. Dohi, T., Beltrami, E., Wall, N. R., Plescia, J., & Altieri, D. C. (2004). Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. *Journal of Clinical Investigation, 114*, 1117–1127.

218. Wang, H. W., Sharp, T. V., Koumi, A., Koentges, G., & Boshoff, C. (2002). Characterization of an anti-apoptotic glycoprotein encoded by Kaposis sarcoma-associated herpesvirus which resembles a spliced variant of human survivin. *EMBO Journal, 21*, 2602–2615.

219. Wang, Z., Jiang, H., Chen, S., Du, F. & Wang, X. (2012) The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. *Cell* 148:228–243.

220. de Almagro, M. C., & Vucic, D. (2012). The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy. *Experimental Oncology, 34*, 200–211.

221. Dubrez, L., Berthelet, J., & Glorian, V. (2013). IAP proteins as targets for drug development in oncology. *Oncology Targeted Therapy, 9*, 1285–1304.

222. Vallabhapurapu, S., Matsuzawa, A., Zhang, W., Tseng, P.-H., Keats, J. J., Wang, H., Vignali, D. A. A., Bergsagel, P. L., & Karin, M. (2008). Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-[kappa]B signaling. *Nature Immunology, 9*, 1364–1370.

223. Varfolomeev, E., Goncharov, T., Maecker, H., Zobel, K., Komuves, L. G., Deshayes, K., & Vucic, D. (2012). Cellular inhibitors of apoptosis are global regulators of NF-κB and MAPK activation by members of the TNF family of receptors. *Science Signaling*, *5*, ra22.

224. Tanabe, O., Akira, S., Kamiya, T., Wong, G. G., Hirano, T., & Kishimoto, T. (1988). Genomic structure of the murine IL-6 gene. High degree conservation of potential regulatory sequences between mouse and human. *Journal of Immunology, 141*, 3875–3881.

225. Xu, S., & Neamati, N. (2013). Gp130: a promising drug target for cancer therapy. *Expert Opinion on Therapeutic Targets, 17*, 1303–1328.

226. Guo, Y., Xu, F., Lu, T., Duan, Z., & Zhang, Z. (2012). Interleukin-6 signaling pathway in targeted therapy for cancer. *Cancer Treatment Reviews, 38*, 904–910.

227. Rokavec, M., Öner, M. G., Li, H., Jackstadt, R., Jiang, L., Lodygin, D., Kaller, M., Horst, D., Ziegler, P. K., Schwitalla, S., Slotta-Huspenina, J., Bader, F. G., Greten, F. R., & Hermeking, H. (2014). IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. *Journal of Clinical Investigation, 124*, 1853–1867.

228. Sullivan, N. J., Sasser, A. K., Axel, A. E., Vesuna, F., Raman, V., Ramirez, N., Oberyszyn, T. M., & Hall, B. M. (2009). Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. *Oncogene, 28*, 2940–2947.

229. Yadav, A., Kumar, B., Datta, J., Teknos, T. N., & Kumar, P. (2011). IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. *Molecular Cancer Research, 9*, 1658–1667.

230. Yu, H., Pardoll, D., & Jove, R. (2009). STATs in cancer inflammation and immunity: a leading role for STAT3. *Nature Reviews Cancer, 9*, 798–809.
231. Grivennikov, S. I., & Karin, M. (2010). Dangerous liaisons: STAT3 and NF-κB collaboration and crosstalk in cancer. *Cytokine and Growth Factor Reviews*, *21*, 11–19.

232. Overall, C. M., & Kleifeld, O. (2006). Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. *Nature Reviews Cancer*, *6*, 227–239.

233. Kessenbrock, K., Plaks, V., & Werb, Z. (2010). Matrix metalloproteinases: regulators of the tumor microenvironment. *Cell*, *141*, 52–67.

234. Bergers, G., Javaherian, K., Lo, K.-M., Folkman, J., & Hanahan, D. (1999). Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. *Science*, *284*, 808–812.

235. Granville, D. J., Carthy, C. M., Jiang, H., Levy, J. G., McManus, B. M., Matroule, J. Y., Piette, J., & Hunt, D. W. C. (2000). Nuclear factor-kappa B activation by the photochemotherapeutic agent verteporfin. *Blood*, *95*, 256–262.

236. Korbelik, M. (2009). Complement upregulation in photodynamic therapy-treated tumors: role of Toll-like receptor pathway and NFkappaB. *Cancer Letters*, *281*, 232–238.

237. Matroule, J. Y., Hellin, A. C., Morliere, P., Fabiano, A. S., Santus, R., Merville, M. P., & Piette, J. (1999). Role of nuclear factor-κB in colon cancer cell apoptosis mediated by aminopyropheophorbide photosensitization. *Photochemistry and Photobiology*, *70*, 540–548.

238. Ryter, S. W. G. C. (1993). Nuclear factor kappa B binding activity in mouse L1210 cells following photofrin II-mediated photosensitization. *Photochemistry and Photobiology*, *58*, 753–756.

239. Volanti, C., Hendrickx, N., Van Lint, J., Matroule, J.-Y., Agostinis, P., & Piette, J. (2005). Distinct transduction mechanisms of cyclooxygenase 2 gene activation in tumour cells after photodynamic therapy. *Oncogene*, *24*, 2981–2991.

240. Du, H., Olivo, M., Mahendran, R., Huang, Q., Shen, H., Ong, C., & Bay, B. (2007). Hypericin photoactivation triggers down-regulation of matrix metalloproteinase-9 expression in well-differentiated human nasopharyngeal cancer cells. *Cellular and Molecular Life Sciences*, *64*, 979–988.

241. Li, B., Chu, X. M., Gao, M. H., & Li, W. X. (2010). Apoptotic mechanism of MCF-7 breast cells in vivo and in vitro induced by photodynamic therapy with C-phycocyanin. *Acta Biochimica et Biophysica Sinica*, *42*, 80–89.

242. Ferrario, A., von Tiehl, K., Wong, S., Luna, M., & Gomer, C. J. (2002). Cyclooxygenase-2 inhibitor treatment enhances photodynamic therapy-mediated tumor response. *Cancer Research*, *62*, 3956–3961.

243. Hendrickx, N., Dewaele, M., Buytaert, E., Marsboom, G., Janssens, S., Boven, M. V., Vandenheede, J. R., de Witte, P., & Agostinis, P. (2005). Targeted inhibition of p38α MAPK suppresses tumor-associated endothelial cell migration in response to hypericin-based photodynamic therapy. *Biochemical and Biophysical Research Communications*, *337*, 928–935.

244. Hendrickx, N., Volanti, C., Moens, U., Seternes, O. M., de Witte, P., Vandenheede, J. R., Piette, J., & Agostinis, P. (2003). Up-regulation of cyclooxygenase-2 and apoptosis resistance by p38 MAPK in hypericin-mediated photodynamic therapy of human cancer cells. *Journal of Biological Chemistry*, *278*, 52231–52239.

245. Makowski, M., Grzela, T., Niderla, J., Łazarczyk, M., Mróz, P., Kopeć, M., Legat, M., Strusińska, K., Koziak, K., Nowis, D., Mrówka, P., Wasik, M., Jakóbisiak, M., & Golab, J. (2003). Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice. *Clinical Cancer Research*, *9*, 5417–5422.

246. Zhou, Q., Olivo, M., Lye, K., Moore, S., Sharma, A., & Chowbay, B. (2005). Enhancing the therapeutic responsiveness of photodynamic therapy with the antiangiogenic agents SU5416 and SU6668 in murine nasopharyngeal carcinoma models. *Cancer Chemotherapy and Pharmacology*, *56*, 569–577.

247. Jee, S. H., Shen, S. C., Chiu, H. C., Tsai, W. L., & Kuo, M. L. (2001). Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency. *Oncogene*, *20*, 198.

248. Gomer, C. J., Luna, M., Ferrario, A., Wong, S., & Gomer, C. (2010). Identification of MAP kinase pathways involved in COX-2 expression following photofrin photodynamic therapy. *Methods in Molecular Biology*, *635*, 47–63.

249. Cogno, I. S., Vittar, N. B. R., Lamberti, M. J., & Rivarola, V. A. (2011). Optimization of photodynamic therapy response by survivin gene knockdown in human metastatic breast cancer T47D cells. *Journal of Photochemistry and Photobiology B*, *104*, 434–443.

250. Ferrario, A., & Gomer, C. J. (2010). Targeting the 90 kDa heat shock protein improves photodynamic therapy. *Cancer Letters*, *289*, 188–194.

251. Ferrario, A., Lim, S., Xu, F., Luna, M., Gaffney, K. J., Petasis, N. A., Schönthal, A. H., & Gomer, C. J. (2011). Enhancement of photodynamic therapy by 2,5-dimethyl celecoxib, a non-cyclooxygenase-2 inhibitor analog of celecoxib. *Cancer Letters*, *304*, 33–40.

252. Ferrario, A., Rucker, N., Wong, S., Luna, M., & Gomer, C. J. (2007). Survivin, a member of the inhibitor of apoptosis family, is induced by photodynamic therapy and is a target for improving treatment response. *Cancer Research*, *67*, 4989–4995.

253. He, G. F., Bian, M. L., Zhao, Y. W., Xiang, Q., Li, H. Y., & Xiao, C. (2009). A study on the mechanism of 5-aminolevulinic acid photodynamic therapy in vitro and in vivo in cervical cancer. *Oncology Reports*, *21*, 861–868.

254. Zhang, M., Yang, J., & Li, F. (2006). Transcriptional and post-transcriptional controls of survivin in cancer cells: novel approaches for cancer treatment. *Journal of Experimental & Clinical Cancer Research: CR*, *25*, 391–402.

255. Du, H., Bay, B.-H., Mahendran, R., & Olivo, M. (2006). Hypericin-mediated photodynamic therapy elicits differential interleukin-6 response in nasopharyngeal cancer. *Cancer Letters*, *235*, 202–208.

256. Brackett, C. M., Owczarczak, B., Ramsey, K., Maier, P. G., & Gollnick, S. O. (2011). IL-6 potentiates tumor resistance to photodynamic therapy (PDT). *Lasers in Surgery and Medicine*, *43*, 676–685.

257. Wang, Q., Horiatis, D., & Pinski, J. (2004). Interleukin-6 inhibits the growth of prostate cancer xenografts in mice by the process of neuroendocrine differentiation. *International Journal of Cancer*, *111*, 508–513.

258. Hatzi, E., Murphy, C., Zoephel, A., Rasmussen, H., Morbidelli, L., Ahorn, H., Kunisada, K., Tontsch, U., Klenk, M., Yamauchi-Takihara, K., Ziche, M., Rofstad, E. K., Schweigerer, L., & Fotsis, L. (2002). N-myc oncogene overexpression down-regulates IL-6; evidence that IL-6 inhibits angiogenesis and suppresses neuroblastoma tumor growth. *Oncogene*, *21*, 3552–3561.

259. Usuda, J., Okunaka, T., Furukawa, K., Tsuchida, T., Kuroiwa, Y., Ohe, Y., Saijo, N., Nishio, K., Konaka, C., & Kato, H. (2001). Increased cytotoxic effects of photodynamic therapy in IL-6 gene transfected cells via enhanced apoptosis. *International Journal of Cancer*, *93*, 475–480.

260. Cheon, Y. K., Cho, Y. D., Moon, J. H., Jang, J. Y., Kim, Y. S., Kim, Y. S., Lee, M. S., Lee, J. S., & Shim, C. S. (2007). Diagnostic utility of interleukin-6 (IL-6) for primary bile duct cancer and changes in serum IL-6 levels following photodynamic therapy. *American Journal of Gastroenterology*, *102*, 2164–2170.

261. Agelopoulos, M., & Thanos, D. (2006). Epigenetic determination of a cell-specific gene expression program by ATF-2 and the histone variant macroH2A. *EMBO Journal*, *25*, 4843–4853.

262. Eferl, R., & Wagner, E. F. (2003). AP-1: a double-edged sword in tumorigenesis. *Nature Reviews Cancer*, *3*, 859–868.
263. Bond, M., Fabunmi, R. P., Baker, A. H., & Newby, A. C. (1998). Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-κB. *FEBS Letters, 435*, 29–34.

264. Filip, A., Clichici, S., Muresan, A., Daicoviciu, D., Tatomir, C., Login, C., Dreve, S., & Gherman, C. (2008). Effects of PDT with 5-aminolevulinic acid and chitosan on Walker carcinosarcoma. *Experimental Oncology, 30*, 212–219.

265. Karrer, S., Bosserhoff, A. K., Weiderer, P., Landthaler, M., & Szeimies, R. M. (2004). Keratinocyte-derived cytokines after photodynamic therapy and their paracrine induction of matrix metalloproteinases in fibroblasts. *British Journal of Dermatology, 151*, 776–783.

266. Osiecka, B., Jurczyszyn, K., Symonowicz, K., Bronowicz, A., Ostasiewicz, P., Czapińska, E., Hotowy, K., Krzystek-Korpacka, M., Gebarowska, E., Izykowska, I., Dziegiel, P., Terlecki, G., & Ziółkowski, P. (2010). In vitro and in vivo matrix metalloproteinase expression after photodynamic therapy with a liposomal formulation of aminolevulinic acid and its methyl ester. *Cellular & Molecular Biology Letters, 15*, 630–650.

267. Almeida Issa, M. C., Piñeiro-Maceira, J., Farias, R. E., Pureza, M., Raggio Luiz, R., & Manela-Azulay, M. (2009). Immunohistochemical expression of matrix metalloproteinases in photodamaged skin by photodynamic therapy. *British Journal of Dermatology, 161*, 647–653.

268. Au, C. M., Luk, S. K., Jackson, C. J., Ng, H. K., Yow, C. M. N., & To, S. S. T. (2006). Differential effects of photofrin, 5-aminolevulinic acid and calphostin C on glioma cells. *Journal of Photochemistry and Photobiology B, 85*, 92–101.

269. Chu, E. S., Wong, T. K., & Yow, C. M. (2008). Photodynamic effect in medulloblastoma: downregulation of matrix metalloproteinases and human telomerase reverse transcriptase expressions. *Photochemistry & Photobiological Sciences, 7*, 76–83.

270. Sharwani, A., Jerjes, W., Hopper, C., Lewis, M. P., El-Maaytah, M., Khalil, H. S. M., MacRobert, A. J., Upile, T., & Salih, V. (2006). Photodynamic therapy down-regulates the invasion promoting factors in human oral cancer. *Archives of Oral Biology, 51*, 1104–1111.

271. Etminan, N., Peters, C., Ficnar, J., Anlasik, S., Bünemann, E., Slotty, P. J., Hänggi, D., Steiger, H.-J., Sorg, R. V., & Stummer, W. (2011). Modulation of migratory activity and invasiveness of human glioma spheroids following 5-aminolevulinic acid-based photodynamic treatment. *Journal of Neurosurgery, 115*, 281–288.

272. Salminen, A., Lehtonen, M., Suuronen, T., Kaarniranta, K., & Huuskonen, J. (2008). Terpenoids: natural inhibitors of NF-κB signaling with anti-inflammatory and anticancer potential. *Cellular and Molecular Life Sciences, 65*, 2979–2999.

273. Coupienne, I., Sb, B., Dewaele, M., Rubio, N., Habraken, Y., Fulda, S., Agostinis, P., & Piette, J. (2011). NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy. *Biochemical Pharmacology, 81*, 606–616.

274. Broekgaarden, M., Kos, M., Jurg, F. A., Van Beek, A. A., Van Gulik, T. M., & Heger, M. (2015). Inhibition of NF-κB in tumor cells exacerbates immune cell activation following photodynamic therapy. *International Journal of Molecular Sciences, 16*, 19960–19977.

275. Chen, H. M., Liu, C. M., Yang, H., Chou, H. Y., Chiang, C. P., & Kuo, M. Y. (2011). 5-Aminolevulinic acid induce apoptosis via NF-κB/JNK pathway in human oral cancer Ca9-22 cells. *Journal of Oral Pathology & Medicine, 40*, 483–489.

276. Rapozzi, V., Umezawa, K., & Xodo, L. E. (2011). Role of NF-κB/Snail/RKIP loop in the response of tumor cells to photodynamic therapy. *Lasers in Surgery and Medicine, 43*, 575–585.

277. Tennant, D. A., Frezza, C., MacKenzie, E. D., Nguyen, Q. D., Zheng, L., Selak, M. A., Roberts, D. L., Dive, C., Watson, D.

G., Aboagye, E. O., & Gottlieb, E. (2009). Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death. *Oncogene, 28*, 4009–4021.

278. Gomer, C. J., Ferrario, A., Luna, M., Rucker, N., & Wong, S. (2006). Photodynamic therapy: combined modality approaches targeting the tumor microenvironment. *Lasers in Surgery and Medicine, 38*, 516–521.

279. Akita, Y., Kozaki, K., Nakagawa, A., Saito, T., Ito, S., Tamada, Y., Fujiwara, S., Nishikawa, N., Uchida, K., Yoshikawa, K., Noguchi, T., Miyaishi, O., Shimozato, K., Saga, S., & Matsumoto, Y. (2004). Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity. *British Journal of Dermatology, 151*, 472–480.

280. Ferrario, A., Fisher, A. M., Rucker, N., & Gomer, C. J. (2005). Celecoxib and NS-398 enhance photodynamic therapy by increasing in vitro apoptosis and decreasing in vivo inflammatory and angiogenic factors. *Cancer Research, 65*, 9473–9478.

281. Harvey, E. H., Webber, J., Kessel, D., & Fromm, D. (2005). Killing tumor cells: the effect of photodynamic therapy using mono-l-aspartyl chlorine and NS-398. *American Journal of Surgery, 189*, 302–305.

282. Lanzo, C. A., Beechem, J. M., Talley, J., & Marnett, L. J. (1998). Investigation of the binding of isoform-selective inhibitors to prostaglandin endoperoxide synthases using fluorescence spectroscopy. *Biochemistry, 37*, 217–226.

283. Luong, C., Miller, A., Barnett, J., Chow, J., Ramesha, C., & B, M. F. (1996). Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2. *Natural Structural Biology, 3*, 927–933.

284. Ulrich, C. M., Bigler, J., & Potter, J. D. (2006). Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. *Nature Reviews Cancer, 6*, 130–140.

285. Futaki, N., Takahashi, S., Yokoyama, M., Arai, I., Higuchi, S., & Otomo, S. (1994). NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro. *Prostaglandins, 47*, 55–59.

286. Kleban, J., Mikeš, J., Szilárdiová, B., Koval', J., Sačková, V., Solár, P., Horváth, V., Hofmanová, J., Kozubík, A., & Fedoročko, P. (2007). Modulation of hypericin photodynamic therapy by pretreatment with 12 various inhibitors of arachidonic acid metabolism in colon adenocarcinoma HT-29 cells. *Photochemistry and Photobiology, 83*, 1174–1185.

287. Chang, C. C., Heller, J. D., Kuo, J., & Huang, R. C. C. (2004). Tetra-O-methyl nordihydroguaiaretic acid induces growth arrest and cellular apoptosis by inhibiting Cdc2 and survivin expression. *Proceedings of the National Academy of Sciences of the United States of America, 101*, 13239–13244.

288. Scheller, J., Garbers, C., & Rose-John, S. (2014). Interleukin-6: from basic biology to selective blockade of pro-inflammatory activities. *Seminars in Immunology, 26*, 2–12.

289. Ferrario, A., Chantrain, C. F., von Tiehl, K., Buckley, S., Rucker, N., Shalinsky, D. R., Shimada, H., DeClerck, Y. A., & Gomer, C. J. (2004). The matrix metalloproteinase inhibitor prinomastat enhances photodynamic therapy responsiveness in a mouse tumor model. *Cancer Research, 64*, 2328–2332.

290. Semenza, G. L. (2007). Evaluation of HIF-1 inhibitors as anticancer agents. *Drug Discovery Today, 12*, 853–859.

291. Ferrario, A., von Tiehl, K. F., Rucker, N., Schwarz, M. A., Gill, P. S., & Gomer, C. J. (2000). Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. *Cancer Research, 60*, 4066–4069.

292. Krieg, R. C., Raupach, K., Ren, Q., Schwamborn, K., & Knuechel, R. (2007). Analyzing effects of photodynamic therapy with 5-aminolevulinic acid (ALA) induced protoporphyrin IX
(PPIX) in urothelial cells using reverse phase protein arrays. *Photochemistry & Photobiological Sciences*, **6**, 1296–1305.

293. Mitra, S., Cassar, S. E., Niles, D. J., Puskas, J. A., Frelinger, J. G., & Foster, T. H. (2006). Photodynamic therapy mediates the oxygen-independent activation of hypoxia-inducible factor 1α. *Molecular Cancer Therapeutics*, **5**, 3268–3274.

294. Moon, J. W., Kim, Y. J., Khwarg, S. I., Chung, H., & Yu, H. G. (2010). Chorioretinal ischemia and angiogenic milieu following photodynamic therapy. *Current Eye Research*, **35**, 314–321.

295. Jiang, B. H., Semenza, G. L., Bauer, C., & Marti, H. H. (1996). Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O₂ tension. *American Journal of Physiology*, **271**, C1172–1180.

296. Bracken, C. P., Whitelaw, M. L., & Peet, D. J. (2003). The hypoxia-inducible factors: key transcriptional regulators of hypoxic responses. *Cellular and Molecular Life Sciences*, **60**, 1376–1393.

297. Denko, N. C. (2008). Hypoxia, HIF1 and glucose metabolism in the solid tumour. *Nature Reviews Cancer*, **8**, 705–713.

298. Schödel, J., Oikonomopoulos, S., Ragoussis, J., Pugh, C. W., Ratcliffe, P. J., & Mole, D. R. (2011). High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq. *Blood*, **117**, e207–e217.

299. Semenza, G. L. (2012). Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. *Trends in Pharmacological Sciences*, **33**, 207–214.

300. Wu, M. Z., Tsai, Y. P., Yang, M. H., Huang, C. H., Chang, S. Y., Chang, C. C., Teng, S. C., & Wu, K. J. (2011). Interplay between HDAC3 and WDR5 is essential for hypoxia-induced epithelial-mesenchymal transition. *Molecular Cell*, **43**, 811–822.

301. Xia, X., Lemieux, M. E., Li, W., Carroll, J. S., Brown, M., Liu, X. S., & Kung, A. L. (2009). Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. *Proceedings of the National Academy of Sciences of the United States of America*, **106**, 4260–4265.

302. Bruick, R. K., & McKnight, S. L. (2001). A conserved family of prolyl-4-hydroxylases that modify HIF. *Science*, **294**, 1337–1340.

303. Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., Tian, Y.-M., Masson, N., Hamilton, D. L., Jaakkola, P., Barstead, R., Hodgkin, J., Maxwell, P. H., Pugh, C. W., Schofield, C. J., & Ratcliffe, P. J. (2001). C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. *Cell*, **107**, 43–54.

304. Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin, W. G., Jr. (2001). HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O₂ sensing. *Science*, **292**, 464–468.

305. Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A., Hebestreit, H. F., Mukherji, M., Schofield, C. J., Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (2001). Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O₂-regulated prolyl hydroxylation. *Science*, **292**, 468–472.

306. Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999). The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. *Nature*, **399**, 271–275.

307. Salceda, S., & Caro, J. (1997). Hypoxia-inducible factor 1α (HIF-1α protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. *Journal of Biological Chemistry*, **272**, 22642–22647.

308. Stiehl, D. P., Wirthner, R., Köditz, J., Spielmann, P., Camenisch, G., & Wenger, R. H. (2006). Increased prolyl 4-hydroxylase

domain proteins compensate for decreased oxygen levels. *Journal of Biological Chemistry*, **281**, 23482–23491.

309. Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C., & Schumacker, P. T. (1998). Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. *Proceedings of National Academy of Sciences U S A*, **95**, 11715–11720.

310. Comito, G., Calvani, M., Giannoni, E., Bianchini, F., Calorini, L., Torre, E., Migliore, C., Giordano, S., & Chiarugi, P. (2011). HIF-1α stabilization by mitochondrial ROS promotes Met-dependent invasive growth and vasculogenic mimicry in melanoma cells. *Free Radical Biology Medicine*, **51**, 893–904.

311. Patten, D. A., Lafleur, V. N., Robitaille, G. A., Chan, D. A., Giaccia, A. J., & Richard, D. E. (2010). Hypoxia-inducible factor-1 activation in nonhypoxic conditions: the essential role of mitochondrial-derived reactive oxygen species. *Molecular Biology of the Cell*, **21**, 3247–3257.

312. Schofield, C. J., & Ratcliffe, P. J. (2004). Oxygen sensing by HIF hydroxylases. *Nature Reviews Molecular Cell Biology*, **5**, 343–354.

313. Lu, H., Dalgard, C. L., Mohyeldin, A., McFate, T., Tait, A. S., & Verma, A. (2005). Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. *Journal of Biological Chemistry*, **280**, 41928–41939.

314. Calvani, M., Comito, G., Giannoni, E., & Chiarugi, P. (2012). Time-dependent stabilization of hypoxia inducible factor-1α by different intracellular sources of reactive oxygen species. *PloS One*, **7**, e38388.

315. Bonello, S., Záhringer, C., BelAiba, R. S., Djordjevic, T., Hess, J., Michiels, C., Kietzmann, T., & Görlach, A. (2007). Reactive oxygen species activate the HIF-1α promoter via a functional NFκB site. *Arteriosclerosis, Thrombosis, and Vascular Biology*, **27**, 755–761.

316. Harris, A. L. (2002). Hypoxia—a key regulatory factor in tumour growth. *Nature Reviews Cancer*, **2**, 38–47.

317. Hirota, K., & Semenza, G. L. (2006). Regulation of angiogenesis by hypoxia-inducible factor 1. *Oncological Hematology*, **59**, 15–26.

318. Weinhouse, S., Warburg, O., Burk, D., & Schade, A. L. (1956). On respiratory impairment in cancer cells. *Science*, **124**, 267–272.

319. Semenza, G. L. (2003). Targeting HIF-1 for cancer therapy. *Nature Reviews Cancer*, **3**, 721–732.

320. Rohwer, N., & Cramer, T. (2011). Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. *Drug Resistance Updates*, **14**, 191–201.

321. Bellot, G., Garcia-Medina, R., Gounon, P., Chiche, J., Roux, D., Pouysségur, J., & Mazure, N. M. (2009). Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. *Molecular and Cellular Biology*, **29**, 2570–2581.

322. An, W. G., Kanekal, M., Simon, M. C., Maltepe, E., Blagoskonny, M.V., Neckers, L. M. (1998). Stabilization of wild-type p53 by hypoxia-inducible factor 1α. *Nature*, **392**, 405–408.

323. Ravi, R., Mookerjee, B., Bhujwalla, Z. M., Sutter, C. H., Artemov, D., Zeng, Q., Dillehay, L. E., Madan, A., Semenza, G. L., Bedi, A. (2000). Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1α. *Genes and Development*, **14**, 34–44.

324. Ji, Z., Yang, G., Shahzidi, S., Tkacz-Stachowska, K., Suo, Z., Nesland, J. M., & Peng, Q. (2006). Induction of hypoxia-inducible factor-1α overexpression by cobalt chloride enhances cellular resistance to photodynamic therapy. *Cancer Letters*, **244**, 182–189.

325. Berra, E., Roux, D., Richard, D. E., & Pouysségur, J. (2001). Hypoxia inducible factor1α (HIF-1α) escapes O2-driven
proteasomal degradation irrespective of its subcellular localization: nucleus or cytoplasm. *EMBO Reports*, *2*, 615–620.

326. Ferrario, A., & Gomer, C. (2006). Avastin enhances photodynamic-ic therapy treatment of Kaposi's sarcoma in a mouse tumor model. *Journal of Environmental Pathology, Toxicology and Oncology*, *25*, 251–260.

327. Koukourakis, M. I., Giatromanolaki, A., Skarlatos, J., Corti, L., Blandamura, S., Piazza, M., Gatter, K. C., & Harris, A. L. (2001). Hypoxia inducible factor (HIF-1α and HIF-2α) expression in early esophageal cancer and response to photodynamic therapy and radiotherapy. *Cancer Research*, *61*, 1830–1832.

328. Mayerhofer, M., Valent, P., Sperr, W. R., Griffin, J. D., & Sillaber, C. (2002). BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1α, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin. *Blood*, *100*, 3767–3775.

329. Luwor, R. B., Lu, Y., Li, X., Mendelsohn, J., & Fan, Z. (2005). The antiepidermal growth factor receptor monoclonal antibody cetuximab/C225 reduces hypoxia-inducible factor-1 alpha, leading to transcriptional inhibition of vascular endothelial growth factor expression. *Oncogene*, *24*, 4433–4441.

330. Majumder, P. K., Febbo, P. G., Bikoff, R., Berger, R., Xue, Q., McMahon, L. M., Manola, J., Brugarolas, J., McDonnell, T. J., Golub, T. R., Loda, M., Lane, H. A., & Sellers, W. R. (2004). mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. *Nature Medicine*, *10*, 594–601.

331. Liu, Y. V., Baek, J. H., Zhang, H., Diez, R., Cole, R. N., & Semenza, G. L. (2007). RACK1 competes with HSP90 for binding to HIF-1α and is required for O₂-independent and HSP90 inhibitor-induced degradation of HIF-1α. *Molecular Cell*, *25*, 207–217.

332. Kaelin, W. G. J., & Ratcliffe, P. J. (2008). Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. *Molecular Cell*, *30*, 393–402.

333. Tennant, D., & Gottlieb, E. (2010). HIF prolyl hydroxylase-3 mediates alpha-ketoglutarate-induced apoptosis and tumor suppression. *Journal of Molecular Medicine (Berlin)*, *88*, 839–849.

334. Bae, M. K., Kim, S. H., Jeong, J. W., Lee, Y. M., Kim, H. S., Kim, S. R., Yun, I., Bae, S. K., & Kim, K. W. (2006). Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1. *Oncology Report*, *15*, 1557–1562.

335. Ströfer, M., Jelkmann, W., & Depping, R. (2011). Curcumin decreases survival of Hep3B liver and MCF-7 breast cancer cells: the role of HIF. *Strahlentherapie und Onkologie*, *187*, 393–400.

336. Heger, M., van Golen, R. F., Broekgaarden, M., & Michel, M. C. (2013). The molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancer. *Pharmacological Reviews*, *66*, 222–307.

337. Ahn, J. C., Kang, J. W., Shin, J. I., & Chung, P. S. (2012). Combination treatment with photodynamic therapy and curcumin induces mitochondria-dependent apoptosis in AMC-HN3 cells. *International Journal of Oncology*, *41*, 2184–2190.

338. Chan, W. H., & Wu, H. J. (2004). Anti-apoptotic effects of curcumin on photosensitized human epidermal carcinoma A431 cells. *Journal of Biological Chemistry*, *92*, 200–212.

339. Hattori, K., Naguro, I., Runchel, C., & Ichijo, H. (2009). The roles of ASK family proteins in stress responses and diseases. *Cell Communication Signal*, *7*, 9.

340. Noguchi, T., Takeda, K., Matsuzawa, A., Saegusa, K., Nakano, H., Gohda, J., Inoue, J., & Ichijo, H. (2005). Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-regulating kinase 1 signalosome is essential for oxidative stress-induced cell death. *Journal of Biological Chemistry*, *280*, 37033–37040.

341. Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K., & Ichijo, H. (1998). Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. *EMBO Journal*, *17*, 2596–2606.

342. Miki, H., & Funato, Y. (2012). Regulation of intracellular signaling through cysteine oxidation by reactive oxygen species. *Journal of Biochemistry*, *151*, 255–261.

343. Fujino, G., Noguchi, T., Matsuzawa, A., Yamauchi, S., Saitoh, M., Takeda, K., & Ichijo, H. (2007). Thioredoxin and TRAF family proteins regulate reactive oxygen species-dependent activation of ASK1 through reciprocal modulation of the N-terminal homophilic interaction of ASK1. *Molecular and Cellular Biology*, *27*, 8152–8163.

344. Ichijo, H. (1999). From receptors to stress-activated MAP kinases. *Oncogene*, *18*, 6087–6093.

345. Minden, A., & Karin, M. (1997). Regulation and function of the JNK subgroup of MAP kinases. *Biochimica et Biophysica Acta*, *1333*, F85–F104.

346. Cuenda, A., & Rousseau, S. (2007). p38 MAP-kinases pathway regulation, function and role in human diseases. *Biochimica et Biophysica Acta*, *1773*, 1358–1375.

347. Mittelstadt, P. R., Salvador, J. M., Fornace, A. J., & Ashwell, J. D. (2005). Activating p38 MAPK: new tricks for an old kinase. *Cell Cycle*, *4*, 1189–1192.

348. Goossens, V., Grooten, J., De Vos, K., & Fiers, W. (1995). Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity. *Proceedings of the National Academy of Sciences of the United States of America*, *92*, 8115–8119.

349. Kim, Y. S., Morgan, M. J., Choksi, S., & Liu, Z. G. (2007). TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death. *Molecular Cell*, *26*, 675–687.

350. Lin, Y., Choksi, S., Shen, H. M., Yang, Q. F., Hur, G. M., Kim, Y. S., Tran, J. H., Nedospasov, S. A., & Liu, Z. G. (2004). Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. *Journal of Biological Chemistry*, *279*, 10822–10828.

351. Roulston, A., Reinhard, C., Amiri, P., & Williams, L. T. (1998). Early activation of c-Jun N-terminal kinase and p38 kinase regulate cell survival in response to tumor necrosis factor α. *Journal of Biological Chemistry*, *273*, 10232–10239.

352. Matsuzawa, A., & Ichijo, H. (2008). Redox control of cell fate by MAP kinase: physiological roles of ASK1-MAP kinase pathway in stress signaling. *Biochimica et Biophysica Acta*, *1780*, 1325–1336.

353. Gupta, S., Barrett, T., Whitmarsh, A. J., Cavanagh, J., Sluss, H. K., Dérijard, B., & D, R. J. (1996). Selective interaction of JNK protein kinase isoforms with transcription factors. *EMBO Journal*, *15*, 2660–2670.

354. Wagner, E. F., & Nebreda, A. R. (2009). Signal integration by JNK and p38 MAPK pathways in cancer development. *Nature Reviews Cancer*, *9*, 537–549.

355. Fuchs, S. Y., Dolan, L., Davis, R. J., & R, Z. (1996). Phosphorylation-dependent targeting of c-Jun ubiquitination by Jun N-kinase. *Oncogene*, *13*, 1531–1535.

356. Jaeschke, A., Karasarides, M., Ventura, J.-J., Ehrhardt, A., Zhang, C., Flavell, R. A., Shokat, K. M., & Davis, R. J. (2006). JNK2 is a positive regulator of the cJun transcription factor. *Molecular Cell*, *23*, 899–911.

357. Yu, R., Chen, C., Mo, Y.-Y., Hebbar, V., Owuor, E. D., Tan, T.-H., & Kong, A. N. T. (2000). Activation of mitogen-activated protein kinase pathways induces antioxidant response element-mediated gene expression via a Nrf2-dependent mechanism. *Journal of Biological Chemistry*, *275*, 39907–39913.

358. Bakiri, L., Lallemand, D., Bossy-Wetzel, E., & Yaniv, M. (2000). Cell cycle-dependent variations in c-Jun and JunB
phosphorylation: a role in the control of cyclin D1 expression. *EMBO Journal*, *19*, 2056–2068.

359. Beier, F., Taylor, A. C., & LuValle, P. (2000). Activating transcription factor 2 is necessary for maximal activity and serum induction of the cyclin A promoter in chondrocytes. *Journal of Biological Chemistry*, *275*, 12948–12953.

360. Katabami, M., Donninger, H., Hommura, F., Leaner, V. D., Kinoshita, I., Chick, J. F. B., & Birrer, M. J. (2005). Cyclin A is a c-Jun target gene and is necessary for c-Jun-induced anchorage-independent growth in RAT1a cells. *Journal of Biological Chemistry*, *280*, 16728–16738.

361. Lewis, J. S., Vijayanathan, V., Thomas, T. J., Pestell, R. G., Albanese, C., Gallo, M. A., & Thomas, T. (2005). Activation of cyclin D1 by estradiol and spermine in MCF-7 breast cancer cells: a mechanism involving the p38 MAP kinase and phosphorylation of ATF-2. *Oncology Research*, *15*, 113–128.

362. Ameyar-Zazoua, M., Wisniewska, M. B., Bakiri, L., Wagner, E. F., Yaniv, M., & Weitzman, J. B. (2005). AP-1 dimers regulate transcription of the p14/p19ARF tumor suppressor gene. *Oncogene*, *24*, 2298–2306.

363. Schreiber, M., Kolbus, A., Piu, F., Szabowski, A., Mühle-Steinlein, U., Tian, J., Karin, M., Angel, P., & Wagner, E. F. (1999). Control of cell cycle progression by c-Jun is p53 dependent. *Genes and Development*, *13*, 607–619.

364. Shaulian, E., & Karin, M. (2001). AP-1 in cell proliferation and survival. *Oncogene*, *20*, 2390–2400.

365. Weitzman, J. B., Fiette, L., Matsuo, K., & Yaniv, M. (2000). JunD protects cells from p53-dependent senescence and apoptosis. *Molecular Cell*, *6*, 1109–1119.

366. Maekawa, T., Sano, Y., Shinagawa, T., Rahman, Z., Sakuma, T., Nomura, S., Licht, J. D., & Ishii, S. (2007). ATF-2 controls transcription of Maspin and GADD45α genes independently from p53 to suppress mammary tumors. *Oncogene*, *27*, 1045–1054.

367. Vale-Cruz, D. S., Ma, Q., Syme, J., & LuValle, P. A. (2008). Activating transcription factor-2 affects skeletal growth by modulating pRb gene expression. *Mechanisms of Development*, *125*, 843–856.

368. Lopez-Bergami, P., Lau, E., & Ronai, Z. (2010). Emerging roles of ATF2 and the dynamic AP1 network in cancer. *Nature Reviews Cancer*, *10*, 65–76.

369. Maekawa, T., Bernier, F., Sato, M., Nomura, S., Singh, M., Inoue, Y., Tokunaga, T., Imai, H., Yokoyama, M., Reimold, A., Glimcher, L. H., & Ishii, S. (1999). Mouse ATF-2 null mutants display features of a severe type of meconium aspiration syndrome. *Journal of Biological Chemistry*, *274*, 17813–17819.

370. Song, H., Ki, S. H., Kim, S. G., & Moon, A. (2006). Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells. *Cancer Research*, *66*, 10487–10496.

371. Herr, I., Posovszky, C., Di Marzio, L., Cifone, M. G., Boehler, T., & Debatin, K. M. (2000). Autoamplification of apoptosis following ligation of CD95-L, TRAIL and TNF-alpha. *Oncogene*, *19*, 4255–4262.

372. Penix, L. A., Sweetser, M. T., Weaver, W. M., Hoeffler, J. P., Kerppola, T. K., & Wilson, C. B. (1996). The proximal regulatory element of the interferon-γ promoter mediates selective expression in T cells. *Journal of Biological Chemistry*, *271*, 31964–31972.

373. Chen, K. D., Hung, J. J., Huang, H. L., Chang, M. D., & Lai, Y. K. (1997). Rapid induction of the Grp78 gene by cooperative actions of okadaic acid and heat-shock in 9L rat brain tumor cells. *European Journal of Biochemistry*, *248*, 120–129.

374. Wen, A. Y., Sakamoto, K. M., & Miller, L. S. (2010). The role of the transcription factor CREB in immune function. *Journal of Immunology*, *185*, 6413–6419.

375. Kasibhatla, S., Brunner, T., Genestier, L., Echeverri, F., Mahboubi, A., & Green, D. R. (1998). DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-κB and AP-1. *Molecular Cell*, *1*, 543–551.

376. Dunn, K. L., Espino, P. S., Drobic, B., He, S., & Davie, J. R. (2005). The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling. *Biochemical Cell Biology*, *83*, 1–14.

377. Sonenberg, N., & Gingras, A. C. (1998). The mRNA 5' cap-binding protein eIF4E and control of cell growth. *Current Opinion in Cell Biology*, *10*, 268–275.

378. Liu, G., Zhang, Y., Bode, A. M., Ma, W. Y., & Dong, Z. (2002). Phosphorylation of 4E-BP1 is mediated by the p38/MSK1 pathway in response to UVB irradiation. *Journal of Biological Chemistry*, *277*, 8810–8816.

379. Wiggin, G. R., Soloaga, A., Foster, J. M., Murray-Tait, V., Cohen, P., & Arthur, J. S. C. (2002). MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts. *Molecular and Cellular Biology*, *22*, 2871–2881.

380. Kyriakis, J. M., & Avruch, J. (2001). Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. *Physiological Reviews*, *81*, 807–869.

381. Huot, J., Houle, F., Marceau, F., & Landry, J. (1997). Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase/heat shock protein 27 pathway in vascular endothelial cells. *Circulation Research*, *80*, 383–392.

382. Moens, U., & Kostenko, S. (2013). Structure and function of MK5/PRAK: the loner among the mitogen-activated protein kinase-activated protein kinases. *Biological Chemistry*, *394*, 1115.

383. Gaestel, M. (2006). MAPKAP kinases—MKs—two's company, three's a crowd. *Nature Reviews Molecular Cell Biology*, *7*, 120–130.

384. Emerling, B. M., Platanias, L. C., Black, E., Nebreda, A. R., Davis, R. J., & Chandel, N. S. (2005). Mitochondrial reactive oxygen species activation of p38 mitogen-activated protein kinase is required for hypoxia signaling. *Molecular and Cellular Biology*, *25*, 4853–4862.

385. Timoshenko, A. V., Chakraborty, C., Wagner, G. F., & Lala, P. K. (2006). COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer. *British Journal of Cancer*, *94*, 1154–1163.

386. Rubio, N., Verrax, J., Dewaele, M., Verfaillie, T., Johansen, T., Piette, J., & Agostinis, P. (2014). p38MAPK-regulated induction of p62 and NBR1 after photodynamic therapy promotes autophagic clearance of ubiquitin aggregates and reduces reactive oxygen species levels by supporting Nrf2-antioxidant signaling. *Free Radical Biological Medicine*, *67*, 292–303.

387. Chang, L., Kamata, H., Solinas, G., Luo, J.-L., Maeda, S., Venuprasad, K., Liu, Y.-C., & Karin, M. (2006). The E3 ubiquitin ligase itch couples JNK activation to TNFα-induced cell death by inducing c-FLIPL turnover. *Cell*, *124*, 601–613.

388. Ventura, J. J., Hübner, A., Zhang, C., Flavell, R. A., Shokat, K. M., & Davis, R. J. (2006). Chemical genetic analysis of the time course of signal transduction by JNK. *Molecular Cell*, *21*, 701–710.

389. Davis, R. J. (2000). Signal transduction by the JNK group of MAP kinases. *Cell*, *103*, 239–252.

390. Inoshita, S., Takeda, K., Hatai, T., Terada, Y., Sano, M., Hata, J., Umezawa, A., & Ichijo, H. (2002). Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress. *Journal of Biological Chemistry*, *277*, 43730–43734.

391. Lei, K., & Davis, R. J. (2003). JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. *Proceedings of the National Academy of Sciences of the United States of America*, *100*, 2432–2437.

392. Lei, K., Nimnual, A., Zong, W. X., Kennedy, N. J., Flavell, R. A., Thompson, C. B., Bar-Sagi, D., & Davis, R. J. (2002). The Bax
subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH2-terminal kinase. *Molecular and Cellular Biology*, **22**, 4929–4942.

393. Liu, J., & Lin, A. (2005). Role of JNK activation in apoptosis: a double-edged sword. *Cell Research*, **15**, 36–42.

394. Buschmann, T., Yin, Z., Bhoumik, A., & Ronai, Z. (2000). Amino-terminal-derived JNK fragment alters expression and activity of c-Jun, ATF2, and p53 and increases H2O2-induced cell death. *Journal of Biological Chemistry*, **275**, 16590–16596.

395. Chen, Y. R., Wang, X., Templeton, D., Davis, R. J., & Tan, T. H. (1996). The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and γ radiation: duration of JNK activation may determine cell death and proliferation. *Journal of Biological Chemistry*, **271**, 31929–31936.

396. Guo, J. S., Cho, C. H., Wang, W. P., Shen, X. Z., Cheng, C. L., & Koo, M. W. (2003). Expression and activities of three inducible enzymes in the healing of gastric ulcers in rats. *World Journal of Gastroenterology*, **9**, 1767–1771.

397. Shen, H. M., Lin, Y., Choksi, S., Tran, J., Jin, T., Chang, L., Karin, M., Zhang, J., & Liu, Z. G. (2004). Essential roles of receptor-interacting protein and TRAF2 in oxidative stress-induced cell death. *Molecular and Cellular Biology*, **24**, 5914–5922.

398. Adler, V., Yin, Z., Fuchs, S. Y., Benezra, M., Rosario, L., Tew, K. D., Pincus, M. R., Sardana, M., Henderson, C. J., Wolf, C. R., Davis, R. J., & Ronai, Z. (1999). Regulation of JNK signaling by GSTp. *EMBO Journal*, **18**, 1321–1334.

399. Elsby, R., Kitteringham, N. R., Goldring, C. E., Lovatt, C. A., Chamberlain, M., Henderson, C. J., Wolf, C. R., & Park, B. K. (2003). Increased constitutive c-Jun N-terminal kinase signaling in mice lacking glutathione S-transferase Pi. *Journal of Biological Chemistry*, **278**, 22243–22249.

400. Thévenin, A. F., Zony, C. L., Bahnson, B. J., & Colman, R. F. (2011). GSTpi modulates JNK activity through a direct interaction with JNK substrate, ATF2. *Protein Sciences*, **20**, 834–848.

401. Wang, T., Arifoglu, P., Ronai, Z., & Tew, K. D. (2001). Glutathione S-transferase P1-1 (GSTP1-1) inhibits c-Jun N-terminal kinase (JNK1) signaling through interaction with the C terminus. *Journal of Biological Chemistry*, **276**, 20999–21003.

402. Yin, Z., Ivanov, V. N., Habelhah, H., Tew, K., & Ronai, Z. (2000). Glutathione S-transferase p elicits protection against H2O2-in- duced cell death via coordinated regulation of stress kinases. *Cancer Research*, **60**, 4053–4057.

403. Gupta, M., Gupta, S. K., Hoffman, B., & Liebermann, D. A. (2006). Gadd45a and Gadd45b protect hematopoietic cells from UV-induced apoptosis via distinct signaling pathways, including p38 activation and JNK inhibition. *Journal of Biological Chemistry*, **281**, 17552–17558.

404. Papa, S., Monti, S. M., Vitale, R. M., Bubici, C., Jayawardena, S., Alvarez, K., De Smaele, E., Dathan, N., Pedone, C., Ruvo, M., & Franzoso, G. (2007). Insights into the structural basis of the GADD45β-mediated Inactivation of the JNK kinase, MKK7/JNKK2. *Journal of Biological Chemistry*, **282**, 19029–19041.

405. Papa, S., Bubici, C., Zazzeroni, F., Pham, C. G., Kuntzen, C., Knabb, J. R., Dean, K., & Franzoso, G. (2006). The NF-[kappa]B-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease. *Cell Death and Differentiation*, **13**, 712–729.

406. Luna, M. C., Wong, S., & Gomer, C. J. (1994). Photodynamic therapy mediated induction of early response genes. *Cancer Research*, **54**, 1374–1380.

407. Tao, J. S., Sanghera, J. S., Pelech, S. L., Wong, G., & Levy, J. G. (1996). Stimulation of stress-activated protein kinase and p38 HOG1 kinase in murine keratinocytes following photodynamic therapy with benzoporphyrin derivative. *Journal of Biological Chemistry*, **271**, 27107–27115.

408. Huang, Y., Minigh, J., Miles, S., & Niles, R. (2008). Retinoic acid decreases ATF-2 phosphorylation and sensitizes melanoma cells to taxol-mediated growth inhibition. *Journal of Molecular Signaling*, **3**, 3.

409. Fisher, G. J., Talwar, H. S., Lin, J., Lin, P., McPhillips, F., Wang, Z., Li, X., Wan, Y., Kang, S., & Voorhees, J. J. (1998). Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo. *Journal of Clinical Investigation*, **101**, 1432–1440.

410. Li, J. J., Dong, Z., Dawson, M. I., & Colburn, N. H. (1996). Inhibition of tumor promoter-induced transformation by retinoids that transrepress AP-1 without transactivating retinoic acid response element. *Cancer Research*, **56**, 483–489.

411. Assefa, Z., Vantieghem, A., Declercq, W., Vandenabeele, P., Vandenheede, J. R., Merlevede, W., de Witte, P., Agostinis, P., The activation of the c-Jun N-terminal kinase and p38 mitogen-activated protein kinase signaling pathways protects HeLa cells from apoptosis following photodynamic therapy with hypericin. *Journal of Biological Chemistry*, **274**, 8788–8796.

412. Xue, L., He, J., Oleinick, N. L. (1999). Promotion of photodynamic therapy-induced apoptosis by stress kinases. *Cell Death and Differentiation*, **6**, 855–864.

413. Tong, Z., Singh, G., Valerie, K., Rainbow, A. J. (2003). Activation of the stress-activated JNK and p38 MAP kinases in human cells by Photofrin-mediated photodynamic therapy. *Journal of Photochemistry and Photobiology B*, **71**, 77–85.

414. Buytaert, E., Matroule, J. Y., Durinck, S., Close, O., Kocanova, S., Vandenheede, J. R., de Witte, P. A., Piette, J., Agostinis, P. (2008). Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells. *Oncogene*, **27**, 1916–1929.

415. Weyergang, A., Kaalhus, O., Berg, K. (2008). Photodynamic therapy with an endocytically located photosensitizer cause a rapid activation of the mitogen-activated protein kinases extracellular signal-regulated kinase, p38, and c-Jun NH2 terminal kinase with opposing effects on cell survival. *Molecular Cancer Therapy*, **7**, 1740–1750.

416. Chan, P. S., Koon, H. K., Wu, Z. G., Wong, R. N. S., Lung, M. L.; Chang, C. K., Mak, N. K. (2009). Role of p38 MAPKs in hypericin photodynamic therapy-induced apoptosis of nasopharyngeal carcinoma cells. *Photochemistry and Photobiology*, **85**, 1207–1217.

417. Tang, P., Zhang, D. M., Xuan, N. H., Tsui, S., Waye, M., Kong, S.-K., Fong, W. P., Fung, K. P. (2009). Photodynamic therapy inhibits p-glycoprotein mediated multidrug resistance via JNK activation in human hepatocellular carcinoma using the photosensitizer phophorbide a. *Molecular Cancer*, **8**, 56.

418. Koon, H. K.; Chan, P. S.; Wu, Z. G.; Wong, R. N. S.; Lung, M. L.; Chang, C. K.; Mak, N. K. (2010). Role of mitogen-activated protein kinase in Zn-BC-AM PDT-induced apoptosis in nasopharyngeal carcinoma cells. *Cell Biochemistry and Function*, **28**, 239–248.

419. Liu, Y., & Chang, A. (2008). Heat shock response relieves ER stress. *EMBO Journal*, **27**, 1049–1059.

420. Hetz, C. (2012). The unfolded protein response: controlling cell fate decisions under ER stress and beyond. *Nature Reviews Molecular Cell Biology*, **13**, 89–102.

421. Dai, C., Dai, S., & Cao, J. (2012). Proteotoxic stress of cancer: implication of the heat-shock response in oncogenesis. *Journal of Cellular Physiology*, **227**, 2982–2987.

422. Helbig, D., Simon, J. C., & Paasch, U. (2011). Photodynamic therapy and the role of heat shock protein 70. *International Journal of Hyperthermia*, **27**, 802–810.

423. Ciocca, D. R., & Calderwood, S. K. (2005). Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. *Cell Stress & Chaperones*, **10**, 86–103.
424. Mann, M. J., & Hendershot, L. M. (2006). UPR activation alters chemosensitivity of tumor cells. *Cancer Biology and Therapy*, *5*, 736–740.

425. Åkerfelt, M., Morimoto, R. I., & Sistonen, L. (2010). Heat shock factors: integrators of cell stress, development and lifespan. *Nature Reviews Molecular Cell Biology*, *11*, 545–555.

426. Park, J., & Liu, A. Y. C. (2001). JNK phosphorylates the HSF1 transcriptional activation domain: role of JNK in the regulation of the heat shock response. *Journal of Biological Chemistry*, *82*, 326–338.

427. Trinklein, N. D., Chen, W. C., Kingston, R. E., & M. R. M. (2004). Transcriptional regulation and binding of heat shock factor 1 and heat shock factor 2 to 32 human heat shock genes during thermal stress and differentiation. *Cell Stress & Chaperones*, *9*, 21–28.

428. Martindale, J. L., & Holbrook, N. J. (2002). Cellular response to oxidative stress: signaling for suicide and survival. *Journal of Cellular Physiology*, *192*, 1–15.

429. Garrido, C., Brunet, M., Didelot, C., Zermati, Y., Schmitt, E., & Kroemer, G. (2006). Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties. *Cell Cycle*, *5*, 2592–2601.

430. Wang, X., Chen, M., Zhou, J., & Z, X. (2014). HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy. *International Journal of Oncology*, *45*, 18–30.

431. Ishikawa, T., Igarashi, T., Hata, K., & Fujita, T. (1999). C-fos induction by heat, arsenite, and cadmium is mediated by a heat shock element in its promoter. *Biochemical and Biophysical Research Communications*, *254*, 566–571.

432. Sawai, M., Ishikawa, Y., Ota, A., & Sakurai, H. (2013). The proto-oncogene JUN is a target of the heat shock transcription factor HSF1. *FEBS Journal*, *280*, 6672–6680.

433. Malhotra, V., & Wong, H.R. (2002). Interactions between the heat shock response and the nuclear factor-κB signaling pathway. *Critical Care Medicine* 30.

434. Saibil, H. (2013). Chaperone machines for protein folding, unfolding and disaggregation. *Nature Reviews Molecular Cell Biology*, *14*, 630–642.

435. Lee, A. H., Iwakoshi, N. N., & Glimcher, L. H. (2003). XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. *Molecular and Cellular Biology*, *23*, 7448–7459.

436. Kincaid, M. M., & Cooper, A. A. (2007). ERADicate ER stress or die trying. *Antioxidants and Redox Signaling*, *9*, 2373–2387.

437. Kadowaki, H., & Nishitoh, H. (2013). Signaling pathways from the endoplasmic reticulum and their roles in disease. *Genes*, *4*, 306–333.

438. Yom, S. S., Busch, T. M., Friedberg, J. S., Wileyto, E. P., Smith, D., Glatstein, E., & Hahn, S. M. (2003). Elevated serum cytokine levels in mesothelioma patients who have undergone pleurectomy or extrapleural pneumonectomy and adjuvant intraoperative photodynamic therapy. *Photochemistry and Photobiology*, *78*, 75–81.

439. Harding, H. P., Zhang, Y., Zeng, H., Novoa, I., Lu, P. D., Calfon, M., Sadri, N., Yun, C., Popko, B., Paules, R., Stojdl, D. F., Bell, J. C., Hettmann, T., Leiden, J. M., & Ron, D. (2003). An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. *Molecular Cell*, *11*, 619–633.

440. Ye, J., & Koumenis, C. (2009). ATF4, an ER stress and hypoxia-inducible transcription factor and its potential role in hypoxia tolerance and tumorigenesis. *Current Molecular Medicine*, *9*, 411–416.

441. He, C. H., Gong, P., Hu, B., Stewart, D., Choi, M. E., Choi, A. M. K., & Alam, J. (2001). Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein: implication for heme oxygenase-1 gene regulation. *Journal of Biological Chemistry*, *276*, 20858–20865.

442. Gomer, C. J., Ryter, S. W., Ferrario, A., Rucker, N., Wong, S., & Fisher, A. M. R. (1996). Photodynamic therapy-mediated oxidative stress can induce expression of heat shock proteins. *Cancer Research*, *56*, 2355–2360.

443. Luna, M. C., Ferrario, A., Wong, S., Fisher, A. M. R., & Gomer, C. J. (2000). Photodynamic therapy-mediated oxidative stress as a molecular switch for the temporal expression of genes ligated to the human heat shock promoter. *Cancer Research*, *60*, 1637–1644.

444. Hanlon, J. G., Adams, K., Rainbow, A. J., Gupta, R. S., & Singh, G. (2001). Induction of Hsp60 by photofrin-mediated photodynamic therapy. *Journal of Photochemistry and Photobiology B*, *64*, 55–61.

445. Korbelik, M., Sun, J., & Cecic, I. (2005). Photodynamic therapy-induced cell surface expression and release of heat shock proteins: relevance for tumor response. *Cancer Research*, *65*, 1018–1026.

446. Mitra, S., Goren, E. M., Frelinger, J. G., & Foster, T. H. (2003). Activation of heat shock protein 70 promoter with meso-tetrahydroxyphenyl chlorin photodynamic therapy reported by green fluorescent protein in vitro and in vivo. *Photochemistry and Photobiology*, *78*, 615–622.

447. Verrico, A. K., & Moore, J. V. (1997). Expression of the collagen-related heat shock protein HSP47 in fibroblasts treated with hyperthermia or photodynamic therapy. *British Journal of Cancer*, *76*, 716–724.

448. Nonaka, M., Ikeda, H., & Inokuchi, T. (2004). Inhibitory effect of heat shock protein 70 on apoptosis induced by photodynamic therapy in vitro. *Photochemistry and Photobiology*, *79*, 94–98.

449. Verrico, A. K., Haylett, A. K., & Moore, J. V. (2001). In vivo expression of the collagen-related heat shock protein HSP47, following hyperthermia or photodynamic therapy. *Lasers in Medical Science*, *16*, 192–198.

450. Wang, H. P., Hanlon, J. G., Rainbow, A. J., Espiritu, M., & Singh, G. (2002). Up-regulation of Hsp27 plays a role in the resistance of human colon carcinoma HT29 cells to photooxidative stress. *Photochemistry and Photobiology*, *76*, 98–104.

451. Ziegler, S. A., Loucks, C., Madsen, S. J., & Carper, S. W. (2007). Heat shock protein 27 protects against aminolevulinic acid-mediated photodynamic therapy-induced apoptosis and necrosis in human breast cancer cells. *Journal of Environmental Pathology, Toxicology and Oncology*, *26*, 173–183.

452. Verfaillie, T., van Vliet, A., Garg, A. D., Dewaele, M., Rubio, N., Gupta, S., de Witte, P., Samali, A., & Agostinis, P. (2013). Pro-apoptotic signaling induced by photo-oxidative ER stress is amplified by Noxa, not Bim. *Biochemical and Biophysical Research Communications*, *438*, 500–506.

453. Garg, A. D., Krysko, D. V., Verfaillie, T., Kaczmarek, A., Ferreira, G. B., Marysael, T., Rubio, N., Firczuk, M., Mathieu, C., Roebroek, A. J. M., Annaert, W., Golab, J., de Witte, P., Vandenabeele, P., & Agostinis, P. (2012). A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. *EMBO Journal*, *31*, 1062–1079.

454. Firczuk, M., Gabrysiak, M., Barankiewicz, J., Domagala, A., Nowis, D., Kujawa, M., Jankowska-Steifer, E., Wachowska, M., Glodkowska-Mrowka, E., Korsak, B., Winiarska, M., & Golab, J. (2013). GRP78-targeting subtilase cytotoxin sensitizes cancer cells to photodynamic therapy. *Cell Death Diseases*, *4*, e741.

455. Miyata, Y. (2005). Hsp90 inhibitor geldanamycin and its derivatives as novel cancer chemotherapeutic agents. *Current Pharmaceutical Design*, *11*, 1131–1138.

456. Taldone, T., Gozman, A., Maharaj, R., & Chiosis, G. (2008). Targeting Hsp90: small-molecule inhibitors and their clinical development. *Current Opinion in Pharmacology*, *8*, 370–374.

457. Jego, G., Hazoumé, A., Seigneuric, R., & Garrido, C. (2013). Targeting heat shock proteins in cancer. *Cancer Letters*, *332*, 275–285.
458. Yoon, Y. J., Kim, J. A., Shin, K. D., Shin, D.-S., Han, Y. M., Lee, Y. J., Lee, J. S., Kwon, B.-M., & Han, D. C. (2011). KRIBB11 inhibits HSP70 synthesis through inhibition of heat shock factor 1 function by impairing the recruitment of positive transcription elongation factor b to the hsp70 promoter. *Journal of Biological Chemistry, 286*, 1737–1747.

459. Li, Z., Agharkar, P., & Chen, B. (2013). Therapeutic enhancement of vascular-targeted photodynamic therapy by inhibiting proteasomal function. *Cancer Letters, 339*, 128–134.

460. Koumenis, C. (2006). ER stress, hypoxia tolerance and tumor progression. *Current Molecular Medicine, 6*, 55–69.