| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Priority Reports |
1 Grupo de Investigación de Enzimología, Departamento de Bioquímica y Biología Molecular A, Facultad de Biología, Universidad de Murcia; 2 Servicio de Análisis Clínicos, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain; and 3 Computational Biology Group and 4 Department of Biological Chemistry, John Innes Centre, Norwich, United Kingdom
Requests for reprints: José Neptuno Rodríguez-López, Grupo de Investigación de Enzimología, Departamento de Bioquímica y Biología Molecular A, Facultad de Biología, Universidad de Murcia, E-30100 Espinardo, Murcia, Spain. Phone: 34-968398284; Fax: 34-968364147; E-mail: neptuno{at}um.es.
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.
Key Words: green tea • catechins • dihydrofolate reductase • EGCG • antifolates
This article has been cited by other articles:
|
|
 |
|
  T. Naganuma, S. Kuriyama, M. Kakizaki, T. Sone, N. Nakaya, K. Ohmori-Matsuda, A. Hozawa, Y. Nishino, and I. Tsuji Green Tea Consumption and Hematologic Malignancies in Japan: The Ohsaki Study Am. J. Epidemiol., September 15, 2009; 170(6): 730 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Shanafelt, T. G. Call, C. S. Zent, B. LaPlant, D. A. Bowen, M. Roos, C. R. Secreto, A. K. Ghosh, B. F. Kabat, M.-J. Lee, et al. Phase I Trial of Daily Oral Polyphenon E in Patients With Asymptomatic Rai Stage 0 to II Chronic Lymphocytic Leukemia J. Clin. Oncol., August 10, 2009; 27(23): 3808 - 3814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Inoue, K. Robien, R. Wang, D. J. Van Den Berg, W.-P. Koh, and M. C. Yu Green tea intake, MTHFR/TYMS genotype and breast cancer risk: the Singapore Chinese Health Study Carcinogenesis, October 1, 2008; 29(10): 1967 - 1972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Zeitlin, I. J. Zeitlin, and J. E. Nor Expanding Circle of Inhibition: Small-Molecule Inhibitors of Bcl-2 as Anticancer Cell and Antiangiogenic Agents J. Clin. Oncol., September 1, 2008; 26(25): 4180 - 4188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Castro, Z. Yu, C. V. Lohr, C. B. Pereira, J. N. Giovanini, K. A. Fischer, G. A. Orner, R. H. Dashwood, and D. E. Williams Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea: primary role of caffeine Carcinogenesis, August 1, 2008; 29(8): 1581 - 1586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-T. Kao, K.-C. Wang, W.-N. Chang, C.-Y. Lin, B.-H. Chen, H.-L. Wu, G.-Y. Shi, J.-N. Tsai, and T.-F. Fu Characterization and Comparative Studies of Zebrafish and Human Recombinant Dihydrofolate Reductases--Inhibition by Folic Acid and Polyphenols Drug Metab. Dispos., March 1, 2008; 36(3): 508 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. van Waalwijk van Doorn-Khosrovani, J. Janssen, L. M. Maas, R. W.L. Godschalk, J. G. Nijhuis, and F. J. van Schooten Dietary flavonoids induce MLL translocations in primary human CD34+ cells Carcinogenesis, August 1, 2007; 28(8): 1703 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Navarro-Martinez, F. Garcia-Canovas, and J. N. Rodriguez-Lopez Tea polyphenol epigallocatechin-3-gallate inhibits ergosterol synthesis by disturbing folic acid metabolism in Candida albicans J. Antimicrob. Chemother., June 1, 2006; 57(6): 1083 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Lucock and P. D. Roach The Antifolate Activity of Tea Catechins Cancer Res., September 15, 2005; 65(18): 8573 - 8573. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
