Table S2 Found at: doi:10.1371/journal.pone.0014700.s003 (0.03 DOC) MB Acknowledgments References We would like to thank Emma Arvidsson for assistance with experiments. 1. Okegawa T, Pong RC, Li Y, Hsieh JT (2004) The role of cell adhesion molecule in cancer progression and its application in cancer therapy. Acta Biochim Pol 51: 445–457. 2. Fukuda H, Sano N, Muto S, Horikoshi M (2006) Simple histone acetylation plays a complex role in the regulation of gene expression. Brief Funct Genomic Proteomic 5: 190–208. 3. Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10: 32–42. 4. Konstantinopoulos PA, Vandoros GP, Papavassiliou AG (2006) FK228 (depsipeptide): a HDAC inhibitor with pleiotropic antitumor activities. Cancer Chemother Pharmacol 58: 711–715. 5. Doi S, Soda H, Oka M, Tsurutani J, Kitazaki T, et al. (2004) The histone deacetylase inhibitor FR901228 induces caspase-dependent apoptosis via the mitochondrial pathway in small cell lung cancer cells. Mol Cancer Ther 3: 1397–1402. 6. Watanabe K, Okamoto K, Yonehara S (2005) Sensitization of osteosarcoma cells to death receptor-mediated apoptosis by HDAC inhibitors through downregulation of cellular FLIP. Cell Death Differ 12: 10–18. 7. Goldsmith ME, Kitazono M, Fok P, Aikou T, Bates S, et al. (2003) The histone deacetylase inhibitor FK228 preferentially enhances adenovirus transgene expression in malignant cells. Clin Cancer Res 9: 5394–5401. 8. Byrd JC, Marcucci G, Parthun MR, Xiao JJ, Klisovic RB, et al. (2005) A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood 105: 959–967. 9. Prince HM, Bishton MJ, Harrison SJ (2009) Clinical studies of histone deacetylase inhibitors. Clin Cancer Res 15: 3958–3969. 10. Molife LR, Attard G, Fong PC, Karavasilis V, Reid AH, et al. (2010) Phase II, two-stage, single-arm trial of the histone deacetylase inhibitor (HDACi) romidepsin in metastatic castration-resistant prostate cancer (CRPC). Ann Oncol 21: 109–113. 11. Zhang Z, Stanfield J, Frenkel E, Kabbani W, Hsieh JT (2007) Enhanced therapeutic effect on androgen-independent prostate cancer by depsipeptide (FK228), a histone deacetylase inhibitor, in combination with docetaxel. Urology 70: 396–401. 12. Kanzaki M, Kakinuma H, Kumazawa T, Inoue T, Saito M, et al. (2007) Low concentrations of the histone deacetylase inhibitor, depsipeptide, enhance the effects of gemcitabine and docetaxel in hormone refractory prostate cancer cells. Oncol Rep 17: 761–767. 13. Sasaki Y, Negishi H, Idogawa M, Suzuki H, Mita H, et al. (2008) Histone deacetylase inhibitor FK228 enhances adenovirus-mediated p53 family gene therapy in cancer models. Mol Cancer Ther 7: 779–787. 14. Goldsmith ME, Aguila A, Steadman K, Martinez A, Steinberg SM, et al. (2007) The histone deacetylase inhibitor FK228 given prior to adenovirus infection can boost infection in melanoma xenograft model systems. Mol Cancer Ther 6: 496–505. 15. Kitazono M, Goldsmith ME, Aikou T, Bates S, Fojo T (2001) Enhanced adenovirus transgene expression in malignant cells treated with the histone deacetylase inhibitor FR901228. Cancer Res 61: 6328–6330. 16. Pong RC, Roark R, Ou JY, Fan J, Stanfield J, et al. (2006) Mechanism of increased coxsackie and adenovirus receptor gene expression and adenovirus uptake by phytoestrogen and histone deacetylase inhibitor in human bladder cancer cells and the potential clinical application. Cancer Res 66: 8822–8828. 17. Watanabe T, Hioki M, Fujiwara T, Nishizaki M, Kagawa S, et al. (2006) Histone deacetylase inhibitor FR901228 enhances the antitumor effect of telomerase-specific replication-selective adenoviral agent OBP-301 in human lung cancer cells. Exp Cell Res 312: 256–265. 18. Pong RC, Lai YJ, Chen H, Okegawa T, Frenkel E, et al. (2003) Epigenetic regulation of coxsackie and adenovirus receptor (CAR) gene promoter in urogenital cancer cells. Cancer Res 63: 8680–8686. 19. Carlsson B, Cheng WS, Totterman TH, Essand M (2003) Ex vivo stimulation of cytomegalovirus (CMV)-specific T cells using CMV pp65-modified dendritic cells as stimulators. Br J Haematol 121: 428–438. 20. Danielsson A, Dzojic H, Nilsson B, Essand M (2008) Increased therapeutic efficacy of the prostate-specific oncolytic adenovirus Ad[I/PPT-E1A] by reduction of the insulator size and introduction of the full-length E3 region. Cancer Gene Ther 15: 203–213. 21. Cheng WS, Kraaij R, Nilsson B, van der Weel L, de Ridder CM, et al. (2004) A novel TARP-promoter-based adenovirus against hormone-dependent and hormone-refractory prostate cancer. Mol Ther 10: 355–364. FK228 Enhances Ad5 Expression Author Contributions Conceived and designed the experiments: AD HD WSC ME. Performed the experiments: AD HD VR. Analyzed the data: AD HD VR. Contributed reagents/materials/analysis tools: WSC. Wrote the paper: AD ME. 22. Loskog A, Dzojic H, Vikman S, Ninalga C, Essand M, et al. (2004) Adenovirus CD40 ligand gene therapy counteracts immune escape mechanisms in the tumor Microenvironment. J Immunol 172: 7200–7205. 23. Leja J, Dzojic H, Gustafson E, Oberg K, Giandomenico V, et al. (2007) A novel chromogranin-A promoter-driven oncolytic adenovirus for midgut carcinoid therapy. Clin Cancer Res 13: 2455–2462. 24. Nilsson M, Ljungberg J, Richter J, Kiefer T, Magnusson M, et al. (2004) Development of an adenoviral vector system with adenovirus serotype 35 tropism; efficient transient gene transfer into primary malignant hematopoietic cells. J Gene Med 6: 631–641. 25. Nilsson M, Karlsson S, Fan X (2004) Functionally distinct subpopulations of cord blood CD34+ cells are transduced by adenoviral vectors with serotype 5 or 35 tropism. Mol Ther 9: 377–388. 26. Valentini A, Biancolella M, Amati F, Gravina P, Miano R, et al. (2007) Valproic acid induces neuroendocrine differentiation and UGT2B7 up-regulation in human prostate carcinoma cell line. Drug Metab Dispos 35: 968–972. 27. Frigo DE, McDonnell DP (2008) Differential effects of prostate cancer therapeutics on neuroendocrine transdifferentiation. Mol Cancer Ther 7: 659–669. 28. Taura K, Yamamoto Y, Nakajima A, Hata K, Uchinami H, et al. (2004) Impact of novel histone deacetylase inhibitors, CHAP31 and FR901228 (FK228), on adenovirus-mediated transgene expression. J Gene Med 6: 526–536. 29. Daniell E, Groff DE, Fedor MJ (1981) Adenovirus chromatin structure at different stages of infection. Mol Cell Biol 1: 1094–1105. 30. Sergeant A, Tigges MA, Raskas HJ (1979) Nucleosome-like structural subunits of intranuclear parental adenovirus type 2 DNA. J Virol 29: 888–898. 31. Tate VE, Philipson L (1979) Parental adenovirus DNA accumulates in nucleosome-like structures in infected cells. Nucleic Acids Res 6: 2769–2785. 32. Chatterjee PK, Vayda ME, Flint SJ (1986) Adenoviral protein VII packages intracellular viral DNA throughout the early phase of infection. EMBO J 5: 1633–1644. 33. Komatsu T, Haruki H, Nagata K (2010) Cellular and viral chromatin proteins are positive factors in the regulation of adenovirus gene expression. Nucleic Acids Res. Epub ahead of print. 34. Yan C, Boyd DD (2006) Histone H3 acetylation and H3 K4 methylation define distinct chromatin regions permissive for transgene expression. Mol Cell Biol 26: 6357–6371. 35. Forsberg O, Carlsson B, Totterman TH, Essand M (2008) Strategic use of an adenoviral vector for rapid and efficient ex vivo-generation of cytomegalovirus pp65-reactive cytolytic and helper T cells. Br J Haematol 141: 188–199. 36. Loskog A, Totterman TH (2007) CD40L - a multipotent molecule for tumor therapy. Endocr Metab Immune Disord Drug Targets 7: 23–28. 37. Malmstrom PU, Loskog AS, Lindqvist CA, Mangsbo SM, Fransson M, et al. (2010) AdCD40L immunogene therapy for bladder carcinoma–the first phase I/ IIa trial. Clin Cancer Res 16: 3279–3287. 38. Dzojic H, Loskog A, Totterman TH, Essand M (2006) Adenovirus-mediated CD40 ligand therapy induces tumor cell apoptosis and systemic immunity in the TRAMP-C2 mouse prostate cancer model. Prostate 66: 831–838. 39. Saukkonen K, Hemminki A (2004) Tissue-specific promoters for cancer gene therapy. Expert Opin Biol Ther 4: 683–696. 40. Ko D, Hawkins L, Yu DC (2005) Development of transcriptionally regulated oncolytic adenoviruses. Oncogene 24: 7763–7774. 41. Cheng WS, Dzojic H, Nilsson B, Totterman TH, Essand M (2006) An oncolytic conditionally replicating adenovirus for hormone-dependent and hormone- independent prostate cancer. Cancer Gene Ther 13: 13–20. 42. Hoshino I, Matsubara H, Akutsu Y, Nishimori T, Yoneyama Y, et al. (2007) Gene expression profiling induced by histone deacetylase inhibitor, FK228, in human esophageal squamous cancer cells. Oncol Rep 18: 585–592. 43. Crabb SJ, Howell M, Rogers H, Ishfaq M, Yurek-George A, et al. (2008) Characterisation of the in vitro activity of the depsipeptide histone deacetylase inhibitor spiruchostatin A. Biochem Pharmacol 76: 463–475. 44. Sowa Y, Orita T, Hiranabe-Minamikawa S, Nakano K, Mizuno T, et al. (1999) Histone deacetylase inhibitor activates the p21/WAF1/Cip1 gene promoter through the Sp1 sites. Ann N Y Acad Sci 886: 195–199. 45. Hoti N, Chowdhury W, Hsieh JT, Sachs MD, Lupold SE, et al. (2006) Valproic acid, a histone deacetylase inhibitor, is an antagonist for oncolytic adenoviral gene therapy. Mol Ther 14: 768–778. PLoS ONE | www.plosone.org 9 February 2011 | Volume 6 | Issue 2 | e14700