14E-27 |
Modulation of arachidonic acid metabolism by a tea catechin, epigallocatechin 3-gallate (EGCG), and its metabolites |
J. HONG1, X. Meng, H. Lu1, C. T. Ho3, and C. S. Yang1. (1) College of Pharmacy, Rutgers, The State Univ. of New Jersey, 125 Susan L. Cullman Lab. for Cancer Research, 164 Frelinghuysen Rd., Piscataway, NJ 08854, (2) Dept. of Food Science, Rutgers, The State Univ. of New Jersey, 65 Dudley Rd., New Brunswick, NJ 08901-8520 Arachidonic acid metabolism is known to be important in inflammatory and carcinogenic processes. Tea constituents have been reported to inhibit both processes. EGCG, the most abundant green tea catechin, is metabolized by methylation and glucuronidation. In the present study, we investigated the effects of EGCG, methyl EGCG, EGCG glucuronides, and theasinensin (an EGCG oxidative dimer) on the release of arachidonic acid metabolites in the HT-29 colon cancer cell system as well as cyclooxygenase (COX)- and 5-lipoxygenase (5-LOX)-dependent arachidonic acid metabolism. At 10 µM, EGCG, 4²-methyl EGCG (MeEGCG), and 4¢,4²-dimethyl EGCG (DiMeEGCG) potently inhibited the release of arachidonic acid metabolites in HT-29 cells (around 70%). Theasinensin and EGCG glucuronides, however, were less effective. EGCG and its metabolites (50 µM) inhibited COX-dependent arachidonic acid metabolism (mainly catalyzed by COX-2) in LPS-stimulated RAW 264.7 cell lysates. EGCG, MeEGCG, DiMeEGCG and EGCG 4²-glucuronide showed similar potency with a 33–37% inhibition. Theasinensin and EGCG 7-glucuronide showed about 10% inhibition. Among several COX-dependent metabolites, prostaglandin D2 formation was most severely inhibited by EGCG and methylated EGCG. EGCG and methylated EGCG also inhibited 5-LOX activity with MeEGCG showing IC50 value less than 10 µM, but theasinensin and EGCG glucuronides were less effective. The results suggest that EGCG and its metabolites affect multiple stages of arachidonic acid metabolism, and the inhibitory activity may contribute to their anti-inflammatory and anti-carcinogenic actions (supported by NIH grants CA56673 and CA88961).
Session 14E, Nutraceuticals & Functional Foods: General I
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