Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound.
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Chemoprevention of colon carcinogenesis by dietary curcumin, a
naturally occurring plant phenolic compound.Rao CV, Rivenson A, Simi
B, Reddy BS.
Division of Nutritional Carcinogenesis, American Health Foundation,
Valhalla, New York 10595.
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 A2, 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. All 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 A2, phospholipase C gamma 1, ex vivo prostaglandin (PG)
E2, 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 A2 (50%) and
phospholipase C gamma 1 (40%) and levels of PGE2 (> 38%). The
formation of prostaglandins such as PGE2, PGF2 alpha, PGD2, 6-keto
PGF1 alpha, and thromboxane B2 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.
PMID: 7812955 [PubMed - indexed for MEDLINE]
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