Cancer prevention properties of tea: Biochemical mechanisms

The major polyphenols in green tea are catechins especially (-)-epigallocatechin-3-gallate (EGCG), while the major flavanols in black tea are theaflavins including theaflavin, theaflavin-3-gallate, theaflavin-3′-gallate, and theaflavin-3,3′-digallate (TDG). The cancer chemopreventive actions of these tea polyphenols have been demonstrated in many animal models. Previous studies indicated that these polyphenols showed non-specific and broad-spectrum anticarcinogenic effects. Recent studies in our laboratory showed that the EGF receptor gene was overexpressed in human A-431 epidermal carcinoma cells. The binding of epidermal growth factor (EOF) to its receptor and autophosphorylation of EGF receptor were inhibited by theaflavins and EGCG. Furthermore, the inducible nitric oxide synthase was suppressed through down-regulating the activation of nuclear factor KB (NFKB) by these polyphenols in macrophages. Among these tea polyphenols, TDG was found to be the most active inhibitor for the EGF-binding to its receptor, autophosphorylation of the receptor, and the activation of NFKB. The growth of these cells was significantly inhibited by theaflavins and EGCG. The mechanisms of this inhibition may be due to the blockade of the mitotic signal transduction through modulating EGF-receptor function, MAP kinase cascades, NFKB activation and c-Jun expression. It has been demonstrated that cancer is the leading cause of death in many countries and it has become, along with cardiovascular and neurodegenerative diseases, the most important issue of modern preventive medicine. Tea is one of the most popular beverages worldwide. Both green tea and black tea have recently attracted attention as naturally occurring cancer preventive agents (1). Tea has three important advantages over some synthetic chemical cancer preventive agents: first, it is nontoxic and available daily to most of the population; second, tea is less expensive and thus is affordable by most people; and third, tea is able to inhibit the development of different types of cancer in various organs according to the of results of animal experiments (2). The anticarcinogenic effects of EGCG and green tea extract on various organs including skin, glandular stomach, duodenum, colon, liver, pancreas and lung in rats and mice have been reported in several laboratories (3-7). The anticarcinogenic effects of black tea extract on skin carcinogenesis and esophageal tumorigenesis in rodents were also reported (8,9). The preventive effects of tea on the cancer development in humans have not been conclusive. Many studies in certain countries had reported no significant association (10,11); in others, a positive association (12,13) and in still others, a negative association between tea consumption and cancer incidence was observed (14-16). A recent study has showed that the slowdown in increase of cancer incidence with age observed among females who consumed more than 10 cups a day is consistent with the finding that increased consumption of green tea is associated with later onset of cancer (17).