Epidemiological case-control studies suggest that polyphenols have anti-cancer effects. Tea has been extensively researched and cell culture studies have shown positive results, but questions remain over the high concentrations needed to elicit effects in cell models. Other polyphenols have also shown anti-cancer effects and the weight of evidence suggests that this effect is real, although mechanisms of action remain unclear. While the antioxidant effects of polyphenols in vitro are fairly well understood, there is less understanding about the in vivo nature of polyphenolic interactions with cell and tissue components. Polyphenols are thought to induce programmed cell death (apoptosis) in cancer cells, which explains their anticancer effects However, cell culture models have shown inconsistent results with polyphenols in an antioxidant role, and in some studies apoptosis is completely stopped by the addition of catalase to the reaction mixture, suggesting that the anti-cancer activity may involve polyphenols in their pro-oxidant form.
The pro-oxidant activity of polyphenols may involve binding to protein kinase C (PKC) at its catalytic unit, which in turn may enhance apoptosis and decrease proliferation. This may occur via inhibition of signal transduction from a separate regulatory unit of PKC, that in turn can be activated by oxidative stress generated from aberrant arachidonic acid metabolism or chemical oxidation. The signal transduction activated by oxidation of the regulatory unit of PKC is likely caused likely by activator protein 1 (AP-1) and nuclear factor κβ (NF- κβ), transcription factors known to be involved in carcinogenesis. Polyphenols, in particular the green tea polyphenol EGCG, may also inhibit the angiogenic effects of vascular endothelial growth factors (VEGF), as well as the metastatic and invasive activity of matrix metalloproteins. In this way polyphenols may be beneficial for their anti-proliferative, anti-apoptotic, anti-angiogenic, anti-invasive, anti-metastatic properties.
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Figure 1. Possible anti-carcinogenic mechanisms of polyphenols. MMPS (matrix metalloproteins), AP-1 (activator protein 1), VEGF (vascular endothelial growth factors). NF-κβ (nuclear factor-κβ).
Lambert. J. D., Hong, J., Yang, G., Liao, J. and Yang, C. S. 2005. Inhibition o carcinogenesis by polyphenols: evidence from laboratory investigations. American Journal of Clinical Nutrition. 91: 284-291
