Bioavailability and stability issues in understanding the cancer preventive effects of tea polyphenols

The cancer preventive activities of tea (Camellia sinensis) have received a great deal of attention from researchers and the general public. The inhibition of carcinogenesis by tea and tea polyphenols has been demonstrated in different animal models of skin, lung, intestinal and other cancer types by many investigators. Numerous mechanisms for the cancer preventive activity have been proposed based on studies of human cancer cell lines without considering the bioavailability of tea polyphenols. The proposed inhibition of mitogen activated protein (MAP) kinases, aberrant arachidonic acid metabolism, nuclear factor κB (NFκB) and activator protein 1 (AP-1) mediated transcription, growth factor-mediated signaling, and other activities could lead to the inhibition of tumor cell growth or induction of apoptosis as well as the inhibition of angiogenesis. In many cases, however, the concentrations of tea polyphenols required to observe these biological effects in vitro exceed the concentrations achievable in blood and tissues by 10- to 100-fold. In addition, in vitro studies are complicated by the fact that tea polyphenols are not stable and reactive oxygen species are generated under most cell culture conditions. It is not clear whether these reactions occur in vivo. From the bioavailability and stability viewpoints, we herein discuss the relevance of in vitro observations to the mechanisms of the cancer preventive activities of tea polyphenols in vivo.