Mechanisms of cancer prevention by tea constituents.

Consumption of tea (Camellia sinensis) has been suggested to prevent cancer, heart disease and other diseases. Animal studies have shown that tea and tea constituents inhibit carcinogenesis of the skin, lung, oral cavity, esophagus, stomach, liver, prostate and other organs. In some studies, the inhibition correlated with an increase in tumor cell apoptosis and a decrease in cell proliferation. Studies with human cancer cell lines have demonstrated that epigallocatechin-3-gallate (EGCG), a major tea polyphenol, inhibits mitogen-activated protein kinases, cyclin-dependent kinases, growth factor-related cell signaling, activation of activator protein 1 (AP-1) and nuclear factor kappaB (NFkappaB), topoisomerase I and matrix metalloproteinases as well as other potential targets. Although some studies report effects of EGCG at submicromolar levels, most experiments require concentrations of >10 or 20 micromol/L to demonstrate the effect. In humans, tea polyphenols undergo glucuronidation, sulfation, methylation, and ring fission. The peak plasma concentration of EGCG is approximately 1 micromol/L. The possible relevance of each of the proposed mechanisms to human cancer prevention is discussed in light of current bioavailability data for tea polyphenols and the potential limitations of animal models of carcinogenesis. Such discussion, it is hoped, will clarify some misunderstandings of cancer prevention by tea and stimulate new research efforts.