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Submitted to: Functional Foods in Health and Disease
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/29/2011 Publication Date: 11/30/2011 Citation: Wang, T.T., Boue, S.M., Krishnan, H.B. 2011. The protective effect of soybean phytochemicals on androgen responsive human prostate cancer cells LNCaP is likely mediated through modulation of hormone/cytokine-dependent pathways. Functional Foods in Health and Disease. 1(11):457-471. Interpretive Summary: Soy contains several phytochemicals that may be responsible for its purported cancer protective effect. Gensistein, daidzein, and its metabolite equol, as well as glyceollins, are all soy–derived phytoalexins that have been proposed to be candidate cancer preventive compounds. The precise effect and mechanism of action of these compounds on prostate cancer is unknown. The present study examined the molecular effects of these soy phytoalexin on cultured human prostate cancer cell LNCaP to elucidate the potential effects on prostate cancer prevention. Soy phytochemicals inhibit growth of androgen responsive prostate cancer cells. Global gene expression analysis using DNA microarray and real time PCR analysis identified multiple pathways affected by soy-derived phytochemicals. These pathways included the androgen receptor-dependent pathway, insulin-like growth factors pathways, and cell cycle-related pathways. Soy-derived phytochemicals appeared to modulate these pathways in a concentration-dependent fashion. Taking into consideration the physiological achievable concentration of soy phytochemicals in the diet, we proposed that the cancer protective effect of these phytoalexins is likely mediated through modulation of hormone/cytokine-dependent pathways. This work provides novel information for cancer research scientist regarding molecular targets and mechanisms of action of soy-derived phytochemicals, and will serve as an important basis for future investigation of targets of cancer cell growth and signaling. This work will benefit basic, as well as translational, research science. Technical Abstract: Population studies suggested that the consumption of a soy rich diet provides protective effects against several chronic diseases including prostate cancer. However, the active components in soy, as well as the mechanisms of action of soy’s protective effects, remain unclear. It would be important to elucidate these questions to support the use of soy in the prevention of chronic disease. A cell culture model and molecular techniques were used as tools to identify a molecular signature induced by soy-derived phytochemicals. Soy phytochemicals inhibit growth of androgen responsive prostate cancer cells. Global gene expression analysis using DNA microarray and real time PCR analysis identified multiple pathways affected by the soy-derived phytochemicals genistein, daidzein, equol, and glyceollins in the androgen responsive human prostate cancer cell LNCaP. These pathways included androgen receptor-dependent pathway, insulin-like growth factors pathways, and cell cycle-related pathways. Soy-derived phytochemicals modulated these pathways in a concentration-dependent fashion. Taking into consideration the physiological achievable concentration of diet-derived soy phytochemicals, we proposed that a concentration-dependent cancer protective effect is likely mediated through modulation of hormone/cytokine-dependent pathways. |
