Inhibition by dietary curcumin of azoxymethane-induced ornithine decarboxylase, tyrosine protein kinase, arachidonic acid metabolism and aberrant crypt foci formation in the rat colon

Abstract

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.

Curcumin enhances the effects of 5‐fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF‐1R

“…[14][15][16][17] Curcumin's chemopreventive effectiveness has also been documented during the promotion/progression phases of colon carcinogenesis. 25,26 One of the important mechanisms of prevention of carcinogenesis by curcumin is downregulation of several cytochrome p-450 enzymes and induction of phase II metabolizing enzymes such as glutathione S-transferase translating into decreased M 1 G DNA adduct formations.…”

“…[14][15][16][17][18] Curcumin has also been shown to prevent the development of adenomas in the intestinal tract of Min1/2 mice, a model of human familial adenomatous polyposis. 19 In a Phase I clinical trial, curcumin has been found to be effective in inhibiting the growth of a variety of tumors.…”

Anticarcinogenic Factors in Plant Foods: A New Class of Nutrients?

“…IP address: 13.66.222.141, on 20 Apr 2019 at 01:12:24, subject to the Cambridge Core terms of use, available absolute requirement for the proliferation of a variety of human tumour cells both in vitro and in vivo (Luk, 1992), and inhibitors of ODC have been shown to deplete polyamine levels and block proliferation in cultured cells (Mamont et al 1976) and in tumours in vivo (Pegg, 1988). It has been proposed that the ability of the flavonoid apigenin to suppress skin tumorigenesis in mice, and of curcumin, a constituent of turmeric, to suppress early markers of tumorigenesis in the rat colon, may be related to reduced ODC levels in the target tissues (Wei et al 1990;Rao et al 1993). Other flavonoids that have been reported to inhibit promoter induced increases in ODC include kaempferol, luteolin, morin and fisetin (Nakadate et al 1984;Fujiki et al 1986).…”

Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex

“…However, it has been shown to be only a very weak direct inhibitor of cyclo-oxygenase enzyme activity (Srivastava and Srimal, 1985). It also has chemopreventive activity in animal models of colon cancer (Rao et al, 1993;Pereira et al, 1996), but its mechanism of action is not well understood. It has been shown to inhibit COX2 expression (Kelley et al, 1996), and in separate studies to be a potent inhibitor of NF-kB activation (Sanjaya and Aggarwal, 1995;Bierhaus et al, 1997;Kumar et al, 1998), but not of its binding to DNA (Bierhaus et al, 1997).…”