Resveratrol Alters The Kinase Activity Of Pkg-I Alpha And Src Family In A2780cp Cells (Ovarian Cancer Cell Line With Mutated P53) Resulting In Growth Inhibition

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Epithelial ovarian cancer is a leading cause of death in gynecological cancer patients. One major hurdle in treating ovarian cancer is drug resistance to commonly-used chemotherapy like cisplatin. Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a natural polyphenol found in foods/drinks like grapes, berries, peanuts and red wine, can inhibit tumor growth. Our lab has previously shown that resveratrol down-regulates expression of protein kinase G type-I (PKG-I) in cancer cells, which correlated with decreased cell proliferation and increased apoptosis. For the present study, we used A2780cp cells, which are cisplatin-resistant epithelial ovarian cancer cells with mutated p53. Our data show that resveratrol did not induce apoptosis even at a higher concentration of 500 µM. However, resveratrol caused concentration-dependent decreases (down to 50% of control levels at 100 µM) of both DNA synthesis and cell adhesion. We also observed a concentration-dependent increase in protein expression levels of PKG-I to 3 times of control levels at 50 µM resveratrol, but a drop at 100 µM resveratrol. Though total Src remained fairly unchanged, pSrcY416 (phosphorylation at tyrosine-416) and pSrcS17 (phosphorylation at serine-17), indicators of Src activation, decreased at 50 and 100 µM resveratrol [assessed by ultrasensitive quantitative NanoPro 1000 (ProteinSimple), a new state-of-the-art capillary electrophoresis-based protein analysis system]. Decreased pSrcY416 levels (44% of control levels at 100 µM resveratrol) suggest that the kinase activity of Src family kinases are decreased at the higher concentrations of resveratrol that cause inhibition of ovarian cancer cell proliferation. These results suggest that resveratrol can be effective in decreasing cell proliferation in chemoresistant ovarian cancer cells and that the mechanism of action of resveratrol may involve a down-regulation of the protein expression levels of PKG-I and the typrosine-kinase activity of Src family of kinases. Citation Format: Priyatham Gorjala, Janica C. Wong, Benjamin F.b Constantino, Mary G. Johlfs, Renee Coffman, Harry Rosenberg, Ronald Fiscus. Resveratrol alters the kinase activity of PKG-Iα and Src family in A2780cp cells (ovarian cancer cell line with mutated p53) resulting in growth inhibition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4558. doi:10.1158/1538-7445.AM2014-4558