Abstract

Abstract Resveratrol (RES), a polyphenolic compound found in the skin of red fruits, exhibits anti-inflammatory, anti-oxidative, anti-cancer, and anti-proliferative characteristics. RES is known to affect nitric oxide (NO) production. NO is produced by nitric oxide synthase, a regulator of innate and adaptive immunity and displays cytostatic and cytotoxic activity against pathogens and cancer cells. Prior reports suggest that RES and NO mediate the killing of cancer cells in vivo as well as in vitro. In this study, we hypothesized that the RES and NO, either alone or synergistically, modulates the molecular mechanisms in murine prostate cancer (PCa) cells. This hypothesis has been tested on mouse PCa cell lines, derived from transgenic adenocarcinoma of mouse prostate (TRAMP), in C57/B6 mice. Interestingly, TRAMP-C1 and TRAMP-C2 are tumorigenic while TRAMP-C3 is non-tumorigenic. TRAMP cells were treated with different concentrations of RES/NO at different time points and analyzed for cell viability/proliferation, cytokines and growth factors production. The results show that the RES/NO-induced molecular mechanisms in TRAMP-C1 and C2 are significantly different while compared to TRAMP-C3 suggesting that TRAMP-C3 cells may use distinct pathways that regulate “eat me” signal in comparison to TRAMP-C1 and C2. This data also demonstrates that RES/NO mode of action is very distinct and exclusive for each TRAMP cell lines in the modulation of molecular pathways.

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