Study of intracellular signals impacted by a green tea standardized extract (Polyphenon E) in cancer cells

Purpose -Green tea consumption has been shown to exhibit cancer-preventive activities in preclinical studies. Polyphenon E (Poly E) is a green tea standardized extract. This study was undertaken to examine the effects of Poly E on PC3 prostate cancer cells and identify the potential signals involved in the anti-proliferative effect of Poly E.Experimental design and results -PC3 prostate cancer cells were used as model system. Treatment of PC3 cells with 30 and 100 μg/ml Poly E significantly decreased cell viability and proliferation, while increasing apoptosis. At all the tested concentrations, Poly E did not exert any antioxidant effect, eliciting instead a pro-oxidant effect at concentrations 30 and 100 μg/ml. The pro-oxidant effect of Poly E is consistent with the observed cytotoxicity, thus establishing a correlation between pro-oxidant activity and the anti-proliferative effect of Poly E in PC3 cells. Furthermore, Poly E-induced cell death was associated with mitochondrial dysfunction in PC3 cells. Exposure of PC3 cells to Poly E caused phospho-Akt inhibition while induced phospho-ERK activation, implicating these two signaling pathways in the observed anti-proliferative effect.Conclusion -Our data indicated a correlation between pro-oxidant activity and anti-proliferative effect Poly E in PC3 cells and suggest ERK and AKT pathways as potential molecular machinery involved in observed phenomena.