Prostate--Cancer--Molecular aspects

Phytochemicals are biologically active secondary plant metabolites that have been shown to exhibit anti-cancer activity. The dietary phytochemicals genistein isoflavone and beta-lapachone, were investigated to determine their effect on the growth of human prostate adenocarcinoma cells in vitro. The cells were exposed to varying concentrations of both phytochemicals in single and combination treatments for specified time periods and their effect was determined using post-treatment cell viability, treatment-induced apoptosis and cell signaling assays. The overall results revealed that both phytochemicals inhibited cell growth and proliferation and induced apoptosis in a dose-dependent manner for both single and combination treatments. However, combination treatments were not significantly more effective than single treatment with either drug. Both phytochemicals could therefore offer therapeutic efficacy in human prostate adenocarcinoma.

The present study was undertaken to determine the chemotherapeutic potential of genistein and beta-lapachone and possible mechanisms of action in prostate cancer in vitro. The bioassays used included: MTT and LDH chemosensitivity-cytotoxicity assays, NQO1 detection, annexin V-FITC, TUNEL and the caspase protease (CPP32) apoptotic detection assays. The results showed that: (i) PC3 cells are sensitive to single and combination treatments in a dose and time dependent manner; (ii) there was treatment-induced dual death pathways (apoptosis and necrosis) with increasing toxicity (necrosis) at higher concentrations in single and combination treatments; (iii) combination treatment was more growth inhibitory than single treatments; (iv) the NQO1 enzyme substantially enhances the toxicity of beta-lapachone but not genistein, while genistein exerted its apoptotic inducing effects via the caspase 3 pathway. The overall results indicate that combination treatments with beta-lapachone and genistein are more efficacious in killing PC3 human prostate cancer cells than treatment with either agent alone.