Cancer chemoprevention with dietary phytochemicals

Key Points Many population-based studies have highlighted the ability of macronutrients and micronutrients in vegetables and fruit to reduce the risk of cancer. Recently, attention has been focused on phytochemicals — non-nutritive components in the plant-based diet that possess cancer-preventive properties. Despite remarkable progress in our understanding of the carcinogenic process, the mechanisms of action of most chemopreventive phytochemicals have not been fully elucidated. Chemopreventive phytochemicals can block initiation or reverse the promotion stage of multistep carcinogenesis. They can also halt or retard the progression of precancerous cells into malignant ones. Many molecular alterations associated with carcinogenesis occur in cell-signalling pathways that regulate cell proliferation and differentiation. One of the central components of the intracellular-signalling network that maintains homeostasis is the family of mitogen-activated protein kinases (MAPKs). Numerous intracellular signal-transduction pathways converge with the activation of the transcription factors NF-κB and AP1. As these factors mediate pleiotropic effects of both external and internal stimuli in the cellular-signalling cascades, they are prime targets of diverse classes of chemopreventive phytochemicals. Basic helix–loop–helix transcription factors such as NRF2 regulate expression of phase II enzymes, which detoxify carcinogens and protect against oxidative stress. A number of phytochemicals have been shown to induce expression of phase II enzymes via NRF2. β-Catenin, a multifunctional protein that was originally identified as a component of cell–cell adhesion machinery, is another important molecular target for chemoprevention. Several dietary phytochemicals have been shown to target this molecule.