Recent studies have strongly indicated that certain daily-consumed dietary phytochemicals could have cancer protective effects against transgenic mice cancer models and cancers mediated by carcinogens, irradiations and carcinogenic metabolites derived from exogenous or endogenous sources. The cancer-protective effects elicited by these dietary compounds are believed to be due at least in part to the induction of cellular defense systems including the detoxifying and antioxidant enzymes system, as well as the inhibition of anti-inflammatory and anti-cell growth signaling pathways culminating in cell cycle arrest and/or cell-death. In this review, we summarize the potential mechanisms including the modulation of nuclear factor kappaB (NF-κB), cyclooxygenases-2 (COX-2), activator protein-1 (AP-1), mitogen-activated protein kinases (MAPKs) and the induction of phase II cellular detoxifying and antioxidant enzymes mediated mainly by the antioxidant response elements (ARE) within the promoter regions of these genes through nuclear factor-erythroid 2-related factor 2 (Nrf2), a member of the Cap ‘n’ collar (CNC) family of the basic region-leucine zipper transcription factor. In addition, we also review several animal models of carcinogenesis and cancer chemopreventive efficacy studies of these animal models using dietary chemopreventive compounds. Finally, we discuss the cellular signaling cascades mediated by Nrf2, NF-κB, AP-1, MAPKs and COX-2, which have been considered to play pivotal roles in tumor initiation, promotion and progression processes, and could be promising molecular targets for the design of drugs targeting cancer prevention and therapy.
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This study was supported in part by Institutional Funds and by RO1-CA094828, RO1-CA092515, RO1-CA073674 and R01-CA118947 to Dr Ah-Ng Tony KONG from the National Institutes of Health (NIH).
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Kwon, K., Barve, A., Yu, S. et al. Cancer chemoprevention by phytochemicals: potential molecular targets, biomarkers and animal models. Acta Pharmacol Sin 28, 1409–1421 (2007) doi:10.1111/j.1745-7254.2007.00694.x
- dietary cancer chemopreventive compounds
- nuclear factor E2-related factor 2
- nuclear factor-kappaB
- activator protein-1
- mitogen-activated protein kinases
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