Inhibition by dietary curcumin of azoxymethane-induced ornithine decarboxylase, tyrosine protein kinase, arachidonic acid metabolism and aberrant crypt foci formation in the rat colon.
The present study was designed to investigate the modulatory role of dietary curcumin on (i) azoxymethane (AOM)-induced ornithine decarboxylase (ODC), tyrosine protein kinase (TPK) and arachidonic acid metabolism in liver and colonic mucosa of male F344 rats, (ii) in vitro arachidonic acid metabolism in the liver and colonic mucosa and (iii) AOM-induced aberrant crypt foci (ACF) formation in the colon of F344 rats. At 5 weeks of age groups of animals were fed one of the experimental diets containing 0 or 2000 p.p.m. curcumin. Two weeks later all the animals except the vehicle-treated groups were given s.c. injections of AOM, 15 mg/kg body wt, once weekly for 2 weeks. The animals intended for biochemical study were killed 5 days later and the colonic mucosa and liver were analyzed for ODC, TPK, lipoxygenase and cyclo-oxygenase metabolites. The animals intended for ACF study were killed 9 weeks later and analyzed for ACF in the colon. The results indicated that in saline-treated animals dietary curcumin significantly inhibited the ODC (P < 0.001) and TPK (P < 0.05) activities in the liver and colonic mucosa. Dietary curcumin significantly decreased the levels of AOM-induced ODC activity in the liver and colon (P < 0.0001) and TPK activity in the liver and colon (P < 0.01-0.0001) and the formation of 5(S)-, 8(S)-, 12(S)- and 15(S)-hydroxyeicosatetraenoic acids (HETEs) in the liver and colon (P < 0.0001). Also, curcumin suppressed AOM-induced prostaglandin (PG) and thromboxane (Tx) formation in the liver (PGE2, PGF2 alpha, PGD2, 6-keto-PGF1 alpha and TxB2 to 40, 59, 55, 53 and 39% respectively) and in the colon (PGE2 and PGF2 alpha to 39 and 41% respectively). Further, dietary curcumin reduced the in vitro formation of HETEs, PGs and Tx in a dose-dependent manner. AOM-induced colonic ACF were significantly (P < 0.001) inhibited in the animals fed the curcumin diet. The results of the present study indicate that curcumin, present in turmeric, inhibits AOM-induced colonic preneoplastic lesions and other cellular events relevant to colon carcinogenesis.
Rao
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Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, NY 10595.
Simi
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B
Reddy
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BS
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001397:Azoxymethane / Q000633:toxicity*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D004790:Enzyme Induction; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008084:Lipoxygenase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D065108:Ornithine Decarboxylase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344
D065108:Ornithine Decarboxylase Inhibitors; D016718:Arachidonic Acid; D008084:Lipoxygenase; D011505:Protein-Tyrosine Kinases; D009955:Ornithine Decarboxylase; D003474:Curcumin; D001397:Azoxymethane