Effects of purified green and black tea polyphenols on cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues.
The effects of green and black tea polyphenols on cyclooxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonic acid metabolism in normal human colon mucosa and colon cancers were investigated. At a concentration of 30 microg/mL, (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin-3-gallate (ECG) from green tea and theaflavins from black 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 formation of thromboxane (TBX) and 12-hydroxyheptadecatrienoic acid (HHT) was decreased to a greater extent than other metabolites. The inhibitory effects of tea polyphenols on COX activity, however, were less pronounced in tumor microsomes than in normal colon mucosal microsomes. Theaflavins strongly inhibited the formation of TBX and HHT, but increased the production of prostaglandin E(2) (PGE(2)) in tumor microsomes. The enhancing effect of theaflavins on PGE(2) production was related to the COX-2 level in the microsomes. Although theaflavin inhibited ovine COX-2, its activity in the formation of PGE(2) was stimulated by theaflavin when ovine COX-2 was mixed with microsomes, suggesting that theaflavin affects the interaction of COX-2 with other microsomal factors (e.g. PGE synthase). The present results indicate that tea polyphenols can affect arachidonic acid metabolism in human colon mucosa and colon tumors, and this action may alter the risk for colon cancer in humans.
Hong
J
J
Laboratory for Cancer Research, College of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
Smith
T J
TJ
Ho
C T
CT
August
D A
DA
Yang
C S
CS
D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D044946:Biflavonoids; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D044946:Biflavonoids; D004791:Enzyme Inhibitors; D005419:Flavonoids; D010636:Phenols; D011108:Polymers; D013662:Tea; C056068:theaflavin; D016718:Arachidonic Acid; D002392:Catechin; C062669:epicatechin gallate; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone