The growth-suppressive effects of farnesol, γ-tocotrienol, genistein, lovastatin and pomegranate extracts individually and in combinations on human prostate tumor cells
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Epidemiological studies indicate that a plant-based diet is associated with reduced cancer risk. The purpose of this research was to study the anti-tumor effects of farnesol, γ-tocotrienol, genistein, pomegranate extracts W (fermented pomegranate juice) and P (pomegranate peel) and the drug lovastatin on the proliferation of human DU145 and LNCaP prostate carcinoma cells and PC-3 prostate adenocarcinoma cells. These study agents except lovastatin are readily available in fruits and vegetables. Farnesol, γ-tocotrienol, genistein, W, P and lovastatin individually induced a dose-dependent suppression of the proliferation of human DU145 and PC-3 prostate carcinoma cells. Farnesol and genistein also induced a dose-dependent suppression of the proliferation of human LNCaP prostate carcinoma cells. Two-agent blends of genistein and γ-tocotrienol, lovastatin and γ-tocotrienol, and extracts W and P suppressed the growth of DU145 cells to a greater extent than the sum of their individual actions, suggesting synergy. Lovastatin at 16 μM inhibited DU145 cell growth by 18%. A two-agent blend of 4 μM lovastatin (4% growth inhibition) and 5 μM γ-tocotrienol (15% growth inhibition) inhibited cell growth by 54%, which is greater than the sum (19%) of their individual inhibitions and three times the growth inhibition (18%) achieved with 16 μM of lovastatin. A three-agent blend of genistein, γ-tocotrienol and lovastatin inhibited PC-3 cells by 83% while the sum of their individual actions totaled a 59% inhibition, again suggesting synergy in their interactions. The concentration (1.5 μM) of the lovastatin in the three-agent blend was half the concentration (3 μM) of lovastatin that individually inhibited the growth of the PC-3 cells by a lesser 75%. Genistein and γ-tocotrienol acting synergistically with lovastatin may lower the drug's effective dose thereby attenuating its associated toxicity. Lowering the effective dose of lovastatin while enhancing its chemotherapeutic potential presents a unique and innovative application to cancer chemotherapy. Additional research is needed to determine how the compounds of this study will affect the normal human prostate cells.