Effects of purified green and black tea polyphenols on cyclooxygenase and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosaand colon tumor tissues

The effects of green and black tea polyphenols on cyclooxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonic acid metabolism in normal human c olon mucosa and colon cancers were investigated. At a concentration of 30 m ug/mL, (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), a nd (-)-epicatechin-3-gallate (ECG) from green tea and theaflavins from blac k tea inhibited LOX-dependent activity by 30-75%. The formation of 5-, 12-, and 15-LOX metabolites was inhibited to a similar extent. Tea polyphenols also inhibited COX-dependent arachidonic acid metabolism in microsomes from normal colon mucosa, with ECG showing the strongest inhibition. The format ion of thromboxane (TBX) and 12-hydroxyheptadecatrienoic acid (HHT) was dec reased to a greater extent than other metabolites. The inhibitory effects o f tea polyphenols on COX activity, however, were less pronounced in tumor m icrosomes than in normal colon mucosal microsomes. Theaflavins strongly inh ibited the formation of TBX and HHT, but increased the production of prosta glandin E-2 (PGE(2)) in tumor microsomes. The enhancing effect of theaflavi ns on PGE(2) production was related to the COX-2 level in the microsomes. A lthough theaflavin inhibited ovine COX-2, its activity in the formation of PGE2 was stimulated by theaflavin when ovine COX-2 was mixed with microsome s, suggesting that theaflavin affects the interaction of COX-2 with other m icrosomal factors (e.g. PGE synthase). The present results indicate that te a polyphenols can affect arachidonic acid metabolism in human colon mucosa and colon tumors, and this action may alter the risk for colon cancer in hu mans. (C) 2001 Elsevier Science Inc. All rights reserved.