CHEMOPREVENTION OF COLON CARCINOGENESIS BY DIETARY CURCUMIN, A NATURALLY-OCCURRING PLANT PHENOLIC COMPOUND

Google Scholar
  • 15 January 1995
    • journal article
    • research article
    • Vol. 55  (2) , 259-266
Abstract
Human epidemiological and laboratory animal model studies have suggested that nonsteroidal antiinflammatory drugs reduce the risk of development of colon cancer and that the inhibition of colon carcinogenesis is mediated through the alteration in cyclooxygenase metabolism of arachidonic acid. Curcumin, which is a naturally occurring compound is present in turmeric, possesses both antiinflammatory and antioxidant properties, and has been tested for its chemopreventive properties in skin and forestomach carcinogenesis. The present study was designed to investigate the chemopreventive action of dietary curcumin on azoxymethane-induced colon carcinogenesis and also the modulating effect of this agent on the colonic mucosal and tumor phospholipase A(2), phospholipase C gamma 1, lipoxygenase, and cyclooxygenase activities in male F344 rats, At 5 weeks of age, groups of animals were fed the control (modified AIN-76A) diet or a diet containing 2000 ppm of curcumin. At 7 weeks of age, all animals, except those in the vehicle (normal saline)-treated groups, were given two weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight. An groups were continued on their respective dietary regimen until the termination of the experiment at 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. Colonic mucosa and tumors were analyzed for phospholipase A(2), phospholipase C gamma 1, ex vivo prostaglandin (PG) E(2), cyclooxygenase, and lipoxygenase activities. The results indicate that dietary administration of curcumin significantly inhibited incidence of colon adenocarcinomas (P < 0.004) and the multiplicity of invasive (P < 0.015), noninvasive (P < 0.01), and total (invasive plus noninvasive) adenocarcinomas (P < 0.001). Dietary curcumin also significantly suppressed the colon tumor volume by >57% compared to the control diet. Animals fed the curcumin diet showed decreased activities of colonic mucosal and tumor phospholipase A(2) (50%) and phospholipase C gamma 1 (40%) and levels of PGE(2), (>38%). The formation of prostaglandins such as PGE(2), PGF(2 alpha), PGD(2), 6-keto PGF(1 alpha), and thromboxane B-2 through the cyclooxygenase system and production of 5(S)-, 8(S)-, 12(S)-, and 15(S) hydroxyeicosatetraenoic acids via the Lipoxygenase pathway from arachidonic acid were reduced in colonic mucosa and tumors of animals fed the curcumin diet as compared to control diet. Although the precise mechanism by which curcumin inhibits colon tumorigenesis remains to be elucidated, it is likely that the chemopreventive action, at least in part, may be related to the modulation of arachidonic acid metabolism.