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- W3166898159 abstract "Resveratrol is a natural plant Nutraceutical that has medicinal effects in the prevention of cancer, aging and other maladies. Our laboratory is interested in determining the mechanism of action of Resveratrol to determine if Resveratrol can also be used in cancer therapy. In our original studies, ovarian cancer cells treated with Resveratrol arrested in S phase with DNA damage checkpoint foci as detected by phosphorylated histone H2AX staining. The entire ATM/ATR checkpoint pathway was activated resulting in direct phosphorylation of H2AX on chromatin and culminating in the inhibition of CDK (cyclin-dependent kinase) activity that drives the cell cycle. Resveratrol is not just activating the checkpoint pathway but also induces DSB (double-stranded DNA breaks) as detected by the #8220;comet#8221; assay. In contrast, normal HFF (human foreskin fibroblasts) were unaffected in all assays. We hypothesize that Resveratrol like radiation damages DNA, which is not repaired efficiently in cancer cells resulting in checkpoint activation and cell cycle arrest. Resveratrol was also found to arrest many different cancer cell lines (Head and Neck, Breast and Ovarian) independently of p53. Resveratrol and a number of similar polyphenols are regulators of the Sirtuin (SIRT) family of protein deacetylases. Because five different polyphenols that can activate Sirtuins also activated the DNA damage checkpoint, both the anti-cancer and anti-aging effects of these plant polyphenols depend on Sirtuin protein deacetylation. Because Resveratrol acts similarly to radiation, Resveratol can be thought of as a non-toxic radiomimetic. In this regard, we propose that Resveratrol will sensitize tumors to the effects of radiotherapy without effecting normal cells or producing side effects. Head and Neck squamous cell carcinoma (HNSCC) is a good model to test the hypothesis because Radiation is used as a treatment for HNSCC but with limited success and with a myriad of side effects. Towards this end, we have found that Resveratrol synergizes with radiation in killing HNSCC cells in vitro at clinically relevant radiation doses. Our current plan includes expanding our in vitro results to in vivo animal xenografts and a clinical feasibility study of the effect of Resveratrol on radiation treatment of HNSCC patients. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3989." @default.
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- W3166898159 date "2009-05-01" @default.
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- W3166898159 title "Abstract #3989: Combined Resveratrol and radiation therapy in head and neck cancer" @default.
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