The antifolate activity of tea catechins

Navarro-Peran, Enma, Durrant, Marcus, Cabezas-Herrera, Juan, Garcia-Canovas, Francisco, Thornley, Roger and Rodriguez-López, José Neptuno (2005) The antifolate activity of tea catechins. Cancer Research, 65 (6). pp. 2059-2064. ISSN 0008-5472

Full text not available from this repository. (Request a copy)
Official URL: http://dx.doi.org/10.1158/0008-5472.CAN-04-3469

Abstract

A naturally occurring gallated polyphenol isolated from green tea leaves, (−)-epigallocatechin gallate (EGCG), has been shown to be an inhibitor of dihydrofolate reductase (DHFR) activity in vitro at concentrations found in the serum and tissues of green tea drinkers (0.1-1.0 μmol/L). These data provide the first evidence that the prophylactic effect of green tea drinking on certain forms of cancer, suggested by epidemiologic studies, is due to the inhibition of DHFR by EGCG and could also explain why tea extracts have been traditionally used in “alternative medicine” as anticarcinogenic/antibiotic agents or in the treatment of conditions such as psoriasis. EGCG exhibited kinetics characteristic of a slow, tight-binding inhibitor of 7,8-dihydrofolate reduction with bovine liver DHFR (KI = 0.109 μmol/L), but of a classic, reversible, competitive inhibitor with chicken liver DHFR (KI = 10.3 μmol/L). Structural modeling showed that EGCG can bind to human DHFR at the same site and in a similar orientation to that observed for some structurally characterized DHFR inhibitor complexes. The responses of lymphoma cells to EGCG and known antifolates were similar, that is, a dose-dependent inhibition of cell growth (IC50 = 20 μmol/L for EGCG), G0-G1 phase arrest of the cell cycle, and induction of apoptosis. Folate depletion increased the sensitivity of these cell lines to antifolates and EGCG. These effects were attenuated by growing the cells in a medium containing hypoxanthine-thymidine, consistent with DHFR being the site of action for EGCG.

Item Type: Article
Additional Information: Durrant's contribution to this multi-author paper was to develop a 3D model for the interaction between epigallocatechin gallate (EGCG) and the dihydrofolate reductase enzyme. We found that EGCG can inhibit the enzyme's normal function, providing an explanation at the molecular level of the anticancer properties of green tea. Reprinted with permission.
Uncontrolled Keywords: Green tea, Epigallocatechin gallate
Subjects: A300 Clinical Medicine
Department: Faculties > Health and Life Sciences > School of Life Sciences > Applied Sciences
Depositing User: EPrint Services
Date Deposited: 22 Dec 2008 11:55
Last Modified: 26 Oct 2015 14:46
URI: http://nrl.northumbria.ac.uk/id/eprint/1137

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics


Policies: NRL Policies | NRL University Deposit Policy | NRL Deposit Licence