Green tea constituent (-)-epigallocatechin-3-gallate inhibits topoisomerase I activity in human colon carcinoma cells

DNA topoisomerases I and II are essential for cell survival and play critic al roles in DNA metabolism and structure. Inhibitors of topoisomerase const itute a novel family of antitumor agents with demonstrated clinical activit y in human malignancies. The clinical use of these agents is limited due to severe toxic effects on normal cells. Therefore, there is a need to develo p novel, nontoxic topoisomerase inhibitors that have the ability to spare n ormal cells. Recent studies have shown that green tea and its major polyphe nolic constituent, epigallocatechin-3-gallate (EGCG), impart growth inhibit ory responses to cancer cells but not to normal cells. Based on the knowled ge that EGCG induces DNA damage, cell cycle arrest, and apoptosis, we consi dered the possibility of the involvement of topoisomerase in the antiprolif erative response of EGCG. Here, for the first time, we show that EGCG inhib its topoisomerase I, but not topoisomerase II in several human colon carcin oma cell lines. Based on this study it is tempting to suggest that combinat ion of EGCG with other conventional topoisomerase inhibitors could be an im proved strategy for treatment of colon cancer. The possible role of EGCG as a chemotherapeutic agent needs to be investigated. (C) 2001 Academic Press .