Chemoprevention of prostate cancer with cruciferous vegetables: Role of epigenetics

Abstract

Globally, prostate cancer is the second most frequently diagnosed cancer in men although the incidence of cancer varies greatly throughout the world. Nutrition and diet are important modifiable risk factors for prostate cancer development. Epidemiological studies have shown an inverse association between cruciferous vegetable intake and the risk of developing prostate cancer. Here we focus specifically on the molecular mechanisms by which phytochemicals in cruciferous vegetables, sulforaphane (SFN), indole-3-carbinol (I3C) and its derivative 3,3′-diindolylmethane (DIM), may prevent the initiation of prostate cancer and slow tumorigenesis. We have particularly emphasized a possible role for epigenetics in this process as many dietary factors can modulate epigenetic alterations and alter susceptibility to disease. We have identified known and possible epigenetic mechanisms by which these phytochemicals can alter detoxification pathways, sex hormone signaling, and genes that regulate cell cycle, apoptosis, inflammation, angiogenesis and metastasis. The ability of SFN, I3C or DIM to target aberrant epigenetic patterns, in addition to their effects on detoxification/carcinogen metabolism, may make them effective chemoprevention agents at multiple stages of the prostate carcinogenesis pathway. The identification of dietary epigenetic modulators and their use either alone or in combination, may increase efficacy of anti-cancer therapies and prevention strategies, without serious side effects.