bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4211: p85alpha mediates p53 K370 acetylation by p300 and regulates its promoter-specific transactivity in the cellular UVB response
Authors: Song Lun , Gao Ming , Dong Wen , Hu Meiru , Li Jingxia , Shi Xiaoyan , Hao Yi , Li Yi , Huang Chuanshu 
Published: July 2012

Abstract
Inducible acetylation of p53 at lysine residues has a great impact on regulating the transactivation of this protein, which is associated with cell growth arrest and/or apoptosis under various stress conditions. However, the factor(s) for regulating p53 acetylation remains largely unknown. In the current study, we have shown that p85α, the regulatory subunit of PI-3K, plays a critical role in mediating p53 acetylation and promoter-specific transactivation in the UVB response. Depletion of p85α in mouse embryonic fibroblasts (MEFs) significantly impairs UVB-induced apoptosis as well as p53 transactivation and acetylation at Lys370 (Lys373 of human p53); however, the accumulation, nuclear translocation and phosphorylation of p53 are not affected. Interestingly, p85α binds to p300, promotes the p300-p53 interaction and the subsequent recruitment of the p53/p300 complex to the promoter region of the specific p53 target gene in response to UVB irradiation. Moreover, ablation of p53 acetylation at Lys370 by site-directed mutagenesis dramatically suppresses UVB-induced expression of the specific p53-responsive gene as well as cell apoptosis. Therefore, we conclude that p85α is a novel regulator of p53-mediated response under certain stress conditions, and targeting the p85α-dependent p53 pathway may be promising for cancer therapy.
Key Words: acetylation/ p85α/ p53/ p300/UVB radiation
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4211. doi:10.1158/1538-7445.AM2011-4211
Abstract 4213: Defining the role of NF-kB as a target for omega-3 fatty acids in prostate cancer
Authors: Whelan Kaitlin A. , Cavazos David , deGraffenried Linda A. 
Published: July 2012

Abstract
Background: Docosahexaenoic acid (DHA), an omega-3 fatty acid, has been shown to enhance anticancer chemotherapies, but the specific mechanisms by which it promotes its anti-cancer effects remain unclear. Recent studies from our laboratory suggest that one important mechanism may be through modulation of NF-κB activity. NF-κB can alter cells by promoting cell proliferation and inflammation, inhibiting apoptosis, and facilitating metastasis. Preliminary data indicate a strong correlation between p65 retention in the cytoplasm and response to omega-3 fatty acids under conditions of androgen deprivation and/or oxidative stress. We hypothesize that regulation of p65 localization in response to cellular stress is an important mechanism by which DHA sensitizes prostate cells to anti-cancer therapies.
Methods: To elucidate the relationship between DHA, NF-κB and prostate cancer, we created a stable LNCaP cell line with constitutively active NF-κB, using a shRNA plasmid to knockout IκBα, the inhibitory protein retaining p65 in the cytoplasm. shRNA was stably transfected into LNCaP cells under G418 drug selection, and NF-κB activity assessed by luciferase reporter assays.
Results: NF-κB activity in the shRNA IκBα knockout clones was four times greater than that in the vector only control clones. Preliminary data suggest that DHA is not as effective at sensitizing cells to therapeutic agents in cells expressing constitutively active NF-κB due to IκBα inhibition compared to cells expressing normally regulated NF-κB. Studies are on-going to further define the role of NF-κB cellular localization in mediating the anti-cancer effects of DHA in prostate cells.
Conclusions: Our preliminary data indicate that cellular localization of the p65 subunit of NF-κB is an important mechanism by which the omega-3 fatty acids DHA sensitize prostate cells to anti-cancer therapies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4213. doi:10.1158/1538-7445.AM2011-4213
Abstract 4217: The anti-malarial compound artesunate induces reactive oxygen species-dependent killing of breast cancer cells
Authors: Greenshields Anna L. , Hoskin David W. 
Published: July 2012

Abstract
Introduction: Artesunate is a semi-synthetic derivative of artemisinin, a natural compound from the herb Artemisia annua L. Artemisinin has been used in traditional Chinese medicine while artesunate has recently been used as an anti-malarial drug. Artesunate is also cytotoxic to human cancer cells. Since the use of artesunate as an anti-malarial agent is associated with few adverse effects, artesunate may represent a less toxic alternative to conventional chemotherapy. This study investigates the cytotoxic effect of artesunate on breast cancer cell lines and the mechanism(s) underlying its activity.
Methods and Results: Artesunate exhibited a time- and dose-dependent cytotoxic effect on all breast carcinoma cell lines examined (MCF-7, T47D, SK-BR-3, MDA-MB-231, MDA-MB-468). Further examination of MDA-MB-468 cells using Oregon Green-488 and Annexin-V-FLUOS/propidium iodide staining indicated that artesunate had an anti-proliferative effect that was associated with apoptosis induction. Cell cycle arrest occurred in the G2 phase, and was evident as early as 24h after artesunate treatment. Artesunate-induced apoptosis was low in normal fibroblasts at concentrations cytotoxic to breast cancer cells, although fibroblast proliferation was inhibited. DiOC6 staining revealed dose-dependent destabilization of the mitochondrial membrane in artesunate-treated MDA-MB-468 cells. Artesunate-treated MDA-MB-468 cells also displayed cytosolic cytochrome c and PARP cleavage, as demonstrated by Western blotting, which was consistent with apoptosis induction. Pretreatment with reduced glutathione rescued MDA-MB-468 cells from artesunate-induced apoptosis, indicating that reactive oxygen species (ROS) mediate artesunate-induced cytotoxicity. In addition, MDA-MB-468 cells that were pretreated with holotransferrin showed increased killing by artesunate, suggesting that iron promotes artesunate-mediated apoptosis. Induction of the endoplasmic reticulum stress pathway in artesunate-treated cells was demonstrated by Western blotting, suggesting involvement of this apoptosis-inducing pathway in artesunate-mediated cytotoxicity.
Conclusions: These data show that artesunate causes reactive oxygen species-dependent induction of apoptosis in breast cancer cells and therefore warrants further investigation as a possible treatment for breast cancer.
Supported by NSERC and the Canadian Breast Cancer Foundation-Atlantic Region
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4217. doi:10.1158/1538-7445.AM2011-4217
Abstract 4218: Guggulsterone controls isomer-specifically TPA-induced MMP-9 expressions of MCF-7 cells: Identification of the cooperative combination of guggulsterone isomers in inhibition of breast cancer invasiveness
Authors: Kim Jong-Suk , Noh Eun-Mi , Kim Jeong-Mi , Lee Young-Rae , Youn Hyun Jo , Jung Sung Hoo , Kim Soo Mi , Park Jinny 
Published: July 2012

Abstract
Guggulsterone [4,17(20)-pregnadiene-3,16-dione], a constituent of Commiphora mukul, is used to treat obesity, diabetes, arthritis, and atherosclerosis. Recently it has been known that guggulesterone isomers (trans or cis) show isomer-specificity in their antileukemic activities in leukemia cells. Here, we investigated whether guggulsterone isomers differently control 12-O-tetradecanoylpho-bol-13-acetate (TPA)-induced MMP-9 expression, and then the combination of these isomers cooperatively inhibits breast cancer invasiveness. Cis-guggulsterone inhibited TPA-induced MMP expression through blocking NF-κB signaling, whereas trans-guggulsterone through blocking MAPK/AP-1 signaling. Cis-guggulsterone was the more potent than trans-guggulsterone in inhibition of TPA-induced MMP-9 expression and cell invasion of MCF-7 cells. Furthermore, we found that the combination of these isomers showed addictive effects on inhibition of cell invasion of MCF-7 cells. These results suggest that guggulesterone controls isomer-specifically TPA-induced MMP-9 expressions and cell invasions of MCF-7 cells. This study is the first to show that combination of guggulsterone isomers might be known as a potential strategy for the medical treatment of breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4218. doi:10.1158/1538-7445.AM2011-4218
Abstract 4222: Induction of apoptosis and cell cycle arrest in renal cancer cells by phenethyl isothiocyanate (PEITC) and the mechanisms involved
Authors: Khan Maruf H. , deGraffenried Linda A. , Sanders Bob G. , Ciolino Henry P. 
Published: July 2012

Abstract
Background: Renal Cell Carcinoma (RCC) has low 5 year survival rate and is resistant to radiation and chemotherapy. Phenethyl Isothiocyanate (PEITC) is a naturally occurring phytochemical that has a variety of anti-cancer properties. Here we explore two anti-cancer properties of PEITC: induction of apoptosis and induction of cell cycle arrest in RCC cell lines and the underlying mechanisms.
Methods: We used two human RCC cell lines Caki-1 and Caki-2. Survival and cell proliferation was assayed using Calcein AM. Annexin V staining was used to measure apoptosis. Caspase-3/7 induction was measured using a fluorescent substrate. Cell Cycle was studied using Propidium Iodide staining. DNA damage was determined using H2AX-γ antibody. Protein expression and phosphorylation was determined using immunoblotting.
Results: PEITC significantly reduced survival of Caki-1 and Caki-2 cells and inhibited their proliferation as determined by Calcein AM. 15 and 20 μM PEITC induced apoptosis (revealed by Annexin V staining) in both cell lines and induced caspase-3/7 activity. Western blot analysis revealed caspase-8, caspase-9 and Bid cleavage suggesting that the apoptosis is mediated through the extrinsic pathway. Lower doses (up to 10 μM) arrested Caki-1 cells in G2/M phase, and this was associated with an increase p38 and MK2 (Thr334) phosphorylation (as revealed by Western Blot). The p38 inhibitor SB203850 inhibited this G2 arrest induced by PEITC. In order to determine if DNA damage was responsible for the apoptosis and G2 arrest, we used an antibody to H2AX-γ phosphorylation. 15 and 20 µM treatment resulted in increased H2AX-γ phosphorylation, but this was completely blocked by caspase-3 inhibitor.
Conclusion: PEITC induces apoptosis in Caki-1 and Caki-2 cells by a mechanism that likely involves the extrinsic pathway. We will use immunoblotting and siRNA to determine which of the extrinsic receptors (DR4, DR5, TRAIL or FAS) is responsible for this apoptosis induction. PEITC does not cause direct DNA damage to the cells; the observed DNA damage is a result of the apoptotic process and is blocked by caspase-3 inhibitors. PEITC induces G2/M arrest in Caki-1 cells and the mechanism is dependent on p38 phosphorylation which activates MK2. Inducing cell cycle arrest and apoptosis may play an important role in the anti-cancer properties of PEITC. Fully understanding the mechanism by which PEITC induces apoptosis and cell cycle arrest in RCC cells may lead to development of novel chemotherapeutic drugs against RCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4222. doi:10.1158/1538-7445.AM2011-4222
Abstract 4223: Possible usefulness of spirulina platensis for supression of some cases of hepatocellular carcinoma, multiple case study
Authors: Hafez Raghda A. , Basha Osama M. , El Ayoty Yassin M. , Sadeq Refaat A. , Dawood Haitham 
Published: July 2012

Abstract
Backgrownd and study aims; One of the most frequent carcinoma through the world is hepato cellular carcinoma (HCC). It is rapidly fatal with a life expectancy of about 6 months from the time of diagnosis. The disease is more prevalent in parts of Africa and Asia with a strong etiological association with viral hepatitis, haemochromatosis, known carcinogen and toxins. There are many therapeutic options for HCC including; surgical operations, chemotherapy, radiofrequency, immune therapy and gene therapy. The use of natural products as drugs is gaining increasing interest especially due to reduced side effects, if any. In this study, we followed up hepatic patients with HCC, taking hot water extract of sterilized blue green alga, spirulina platenesis. Seven volunteers with cirrhotic liver resulting from chronic viral C hepatitis that had developed HCC were followed up in this work. All available investigations including laboratory and imaging facilities were done before starting the study and repeated monthly for follow up during the study.Results; After 10-15 months, patients are still alive, showing an improvement in the general condition with an obvious regression of the tumor size as well as, better liver functions. Also no obvious side effects were detected during the study.Conclusion; These observations may direct our attentions towards the possibility that the “water extract of sterilized blue green algae; spirulina platenesis” may be of therapeutic value in treatment and/or amelioration of symptoms of hepato cellular carcinoma especially in cirrhotic patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4223. doi:10.1158/1538-7445.AM2011-4223
Abstract 4226: Curcumin induced CaSR stimulates calpain autolysis in colon cancer
Authors: Singh Vinay K. , Kelly Jacqueline C. , MacLeod R John , Jia Zongchao 
Published: July 2012

Abstract
Colon cancer is the fourth most common form of cancer in the United States and the third leading cause of cancer-related death in the Western world. Progression to colon cancer is distinguished with a loss of the colonic calcium sensing receptor (CaSR). It has been observed that calcium-dependent proteolytic enzyme, Calpain (Capn) overexpressed in colon cancer may contribute to its metastasis. We attempted to identify role of calcium sensing receptor CaSR on regulation of capn activity and its influence on calmodulin (CaM) homeostasis. We have also investigated the role of curcumin in activation of CaSR. Curcumin (1μM and 20μM) increases expression (qPCR) and protein (2-3 fold) of the CaSR in wild type intestinal cells (RKO; wild type APC, wild type β-catenin) and cells with truncated APC (HT-29, SW480). Transient transfection of siRNA (200 nM) duplex against CaSR reduced CaSR protein expression and prevented reduction of Capn activity after 3 mM Ca2+ challenge (340+/-24 Units, p&lt;0.05 n=4). Western blotting of HT-29 cell lysates after 3 mM Ca2+ challenge demonstrated no change in amount of Calpain-4 (Capn4, small subunit of Capn essential for its activity) but a 6 fold increase in CaM. Bioinformatic analysis of Capn4 revealed a presence of putative CaM binding site. Using circular dichroism, isothermal titration calorimetry and nuclear magnetic resonance it was confirmed that Capn4 binds to CaM. This is a first report of its kind demonstrating interaction of two EF-hand proteins. Capn after 30 min incubation with CaM demonstrated a 3 fold increase in autolysed Capn and 5 fold reduction in 75 kDa large-subunit of Capn. CaM antagonists W7 or W13 (100 μM) prevented CaSR-mediated decrease in Calpain activity (p&lt;0.05, n=4). We hereby conclude that curcumin will increase CaSR expression and that calcium will stimulate the CaSR to increase calmodulin in colonic adenocarcinoma to produce Capn autolysis which will reduce Capn activity. We speculate that CaSR-mediated reduction in Capn activity may be an important determinant of calcium chemoprevention of colon cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4226. doi:10.1158/1538-7445.AM2011-4226
Abstract 4227: Curcumin in cyclodextrin in liposome as a delivery vehicle against osteosarcoma
Authors: Dhule Santosh S. , Penfornis Patrice , Frazier Trivia , Walker Ryan , Tan Grace , He Jibao , John Vijay , Pochampally Radhika 
Published: July 2012

Abstract
The delivery of curcumin, a broad spectrum anticancer drug, has been explored in the form of liposomal nanoparticles to treat osteosarcoma. Osteosarcoma (OS) accounts for approximately 20% of all bone cancers and it develops during the period of rapid growth in adolescence. Anti-cancer potential of curcumin has not been fully explored in the form of nanoformulations against OS. The drug is water insoluble and an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Liposomal curcumin's potential evaluated against OS and breast cancer. The resulting 2-Hydroxypropyl-gamma-cyclodextrin/curcumin-liposome complex shows promising anticancer potential against cancer of mesenchymal and epithelial origin when tested against KHOS and MCF-7 cell lines with IC50 value of 5.4 and 10.2 µg/ml respectively. The anticancer potential of curcumin in the form of DCL (drug-in-cyclodextrin-in-liposome) preparation has been explored first time for OS. DMSO-curcumin (free drug) induced autophagic cell death in KHOS whereas liposomal curcumin initiates the caspase cascade that leads to apoptotic cell death in vitro and in vivo also. The in vivo study was performed using human osteosarcoma xenograft model in mice. Interestingly, liposomal curcumin was less toxic on normal cells. In this study, the objective to cause cancer cell death by apoptosis and not by autophagy was achieved through liposomal curcumin formulations alone.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4227. doi:10.1158/1538-7445.AM2011-4227
Abstract 423: Decipher the molecular mechanisms by which syndecan-1 in breast cancer stroma fibroblasts regulates extracellular matrix fiber organization and carcinoma cell motility
Authors: Yang Ning , Friedl Andreas 
Published: July 2012

Abstract
The cell surface proteoglycan syndecan-1 (Sdc1) is frequently induced in the stromal fibroblasts of invasive breast carcinomas. We have recently identified a striking correlation between stromal Sdc1 expression and extracellular matrix (ECM) fiber architecture, both In vivo (in human breast carcinoma samples) and in vitro. Bioactive, cell-free 3D ECMs generated from cultures of Sdc1-positive human mammary fibroblasts (HMF), termed ECM-Sdc1, showed an organized, aligned fiber architecture, which contrasted markedly with the random fiber arrangement seen in the ECM of Sdc1-negative HMFs (ECM-mock). We further demonstrated that aligned ECM fiber architecture was responsible for the enhanced directional migration and invasion of the breast carcinoma cells when seeded into the fibroblast-free ECM-Sdc1.
To decipher the molecular mechanisms responsible for the formation of an invasion-permissive ECM, a series of Sdc1 mutants was introduced into HMF. These include a heparan sulfate (HS) -deficient, a cytoplasmic domain (CD) deletion and a transmembrane domain (TMD) substitution mutant. Early experiments suggest that HS are required for the activity of Sdc1 in regulating ECM alignment, while TDM is dispensable.
Integrins play a key role in the assembly of the provisional fibronectin-rich ECM and Sdc1 has been shown to be an important regulator of integrin activity. Therefore, we have begun to investigate the the role of integrins in Sdc1-mediated ECM fiber alignment. HMF expresses various integrins, as determined by Western blotting and flow cytometry. Using siRNA oligos, we are targeting different integrin subunits including α4, α5, αV and β3 to determine, which integrins are responsible for Sdc1-dependent ECM fiber alignment and consequently the invasion-permissive properties of the ECM. A better understanding of the mechanisms governing ECM organization may lead to the development of novel stroma-targeted therapy for breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 423. doi:10.1158/1538-7445.AM2011-423
Abstract 4230: Anthocyanins from the fruit of Vitis coignetiae Pulliat exhibits anticancer effects on Hep 3B human hepatocelluar carcinoma cells xenografts in nude mice
Authors: Lu Jing Nan , Jeong Kim Min , Lee Won Sup , Yun Jeong Won , Kim Dong Chul , Lee Yun Koung , Jeong Jae-Hoon , Choi Yung Hyun , Kim GonSup , Ryu Chung Ho , Park Ock Jin , Shin Sung Chul 
Published: July 2012

Abstract
Vitis coignetiae Pulliat (Meoru in Korea) has been used as a folk remedy for inflammatory diseases and cancers. Our previous in vitro study suggested that anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) should have anti-cancer activities through suppression of NF-κB. Before in vivo study, we also confirmed with Hep3B human hepatocellular carcinoma cells that AIMs suppressed NF-κB-regulated gene products. Here, we investigated their effects on NF-κB-regulated gene products and cellular responses in Hep3B cell-originated tumors in athymic nude mice. Hep3B cells (1 × 106 cells/0.1 mL) were subcutaneously injected into the left flank of twelve athymic (nu/nu) male nude mice, and then the nude mice were randomly divided into two groups with six animals each. The first group of animals received intraperitoneal injection of 100 AL of 1:10 ratio of DMSO and normal saline, whereas animals of the second group received intraperitoneal injection of AIMs (5 μg/g of animal in 100 AL of 1:10 ratio of DMSO and normal saline) daily. The AIMs suppressed the tumor growth compared to control. AIMs suppressed Ki67 expression and intratumoral vessel density on immunohistochemical staining. In addition, Western blot and immunohistochemical staining revealed AIMs suppressed the NF-KB activation and NF-KB-regulated protein levels such as COX-2, XIAP, MMP-9, VEGF and ICAM which are related to cancer cell proliferation, survival, invasion and angiogenesis in Hep3B cell-originated tumors in athymic nude mice. However, the expressions of some NF-KB-regulated proteins were not significantly suppressed.
Taken together, this study indicates that the AIMs have anti-cancer effects on Hep3B cell xenografts at least in part through the inhibition of NF-κB activation and downstream proteins. This study provides evidence that AIMs might have anticancer effects on human hepatocellular carcinoma. [This study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare & Family Affairs, Republic of Korea. (0820050).]
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4230. doi:10.1158/1538-7445.AM2011-4230