Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer.
Curcumin, derived from the rhizome of Curcuma longa L. and having both antioxidant and anti-inflammatory properties, inhibits chemically induced carcinogenesis in the skin, forestomach, and colon when it is administered during initiation and/or postinitiation stages. This study was designed to investigate the chemopreventive action of curcumin when it is administered (late in the premalignant stage) during the promotion/progression stage of colon carcinogenesis in male F344 rats. We also studied the modulating effect of this agent on apoptosis in the tumors. At 5 weeks of age, groups of male F344 rats were fed a control diet containing no curcumin and an experimental AIN-76A diet with 0.2% synthetically derived curcumin (purity, 99.9%). At 7 and 8 weeks of age, rats intended for carcinogen treatment were given s.c. injections of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight per week. Animals destined for the promotion/progression study received the AIN-76A control diet for 14 weeks after the second AOM treatment and were then switched to diets containing 0.2 and 0.6% curcumin. Premalignant lesions in the colon would have developed by week 14 following AOM treatment. They continued to receive their respective diets until 52 weeks after carcinogen treatment and were then sacrificed. The results confirmed our earlier study in that administration of 0.2% curcumin during both the initiation and postinitiation periods significantly inhibited colon tumorigenesis. In addition, administration of 0.2% and of 0.6% of the synthetic curcumin in the diet during the promotion/progression stage significantly suppressed the incidence and multiplicity of noninvasive adenocarcinomas and also strongly inhibited the multiplicity of invasive adenocarcinomas of the colon. The inhibition of adenocarcinomas of the colon was, in fact, dose dependent. Administration of curcumin to the rats during the initiation and postinitiation stages and throughout the promotion/progression stage increased apoptosis in the colon tumors as compared to colon tumors in the groups receiving AOM and the control diet. Thus, chemopreventive activity of curcumin is observed when it is administered prior to, during, and after carcinogen treatment as well as when it is given only during the promotion/progression phase (starting late in premalignant stage) of colon carcinogenesis.
Kawamori
T
T
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, New York 10595, USA.
Lubet
R
R
Steele
V E
VE
Kelloff
G J
GJ
Kaskey
R B
RB
Rao
C V
CV
Reddy
B S
BS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D003474:Curcumin / Q000627:therapeutic use*; D004032:Diet; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D008297:Male; D011230:Precancerous Conditions / Q000188:drug therapy; D051381:Rats; D011916:Rats, Inbred F344