Potential mechanism of phytochemical-induced apoptosis in human prostate cancer cells: Genistein and beta-lapachone

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.