Molecular targets for cancer prevention by tea polyphenols.

A85

Many studies have shown the inhibitory effect of green and black tea against carcinogenesis in rodent models. These include models for cancers of skin, lung, esophagus, stomach, liver, duodenum, small intestine, pancreas and mammary gland. Different tea preparations contain varying amounts of tea polyphenols, among which epigallocatechin 3-gallate (EGCG) is the most well studied and is believed to be the most potent active anti-cancer tea polyphenol. Even though multiple mechanisms of action have been proposed, the molecular basis of the chemopreventive effect of tea polyphenols is still not clear. Searching for the EGCG "target" or high affinity proteins that bind to EGCG is the first step in understanding the molecular and biochemical mechanism of the anticancer effects of tea polyphenols. Recently, we and other few groups have identified a few of these EGCG-binding proteins, including plasma proteins: vimentin, GRP78, JNK, fibronectin, fibrinogen, and histidine-rich glycoprotein, laminin, and the 67-kDa laminin receptor. We have studied the biologic and physiologic significance of these proteins for the anticancer effects of tea polyphenols. These newly identified EGCG-binding proteins should facilitate the design of new strategies to prevent cancer.