Aging alters the inhibition of colonic aberrant crypt foci by curcumin

Curcumin, the yellow pigment of the rhizome of Cucuma longa Linn., has antioxidative, anti-inflammatory and chemopreventive activities. The effect of aging on the inhibition of early-stage colon cancer by curcumin was examined in young (6 wk), mature (12 mo) and old (22 mo) Sprague-Dawley male rats. Rats in each age group were fed either the AIN-93 containing 0.6% curcumin or AIN-93 control diet. Aberrant crypt foci (ACF) were induced by two weekly subcutaneous injections of azoxymethane (15 mg/kg body). After an additional 3 mo of consuming the diets, the number, multiplicity (number of crypts per foci) and distribution of ACF were evaluated. In rats fed the AIN-93 control diet, the number of ACF with a multiplicity [greater than or equal to] 2 was 100.3 [+ or -] 28.1 in young rats, 76.2 [+ or -] 32.7 in mature rats and 76.7 [+ or -] 19.8 in old rats. Addition of curcumin to the diet reduced the number of ACF to 51.0 [+ or -] 14.5 (49% reduction) in young rats and 34.7 [+ or -] 15.0 (55% reduction) in old rats. However, surprisingly, no reduction of ACF (78.5 [+ or -] 28.0) was found in mature rats fed curcumin. Inhibition of large ACF also appeared to be affected by age, with the greatest reduction of large ACF occurring in old rats. Distribution of ACF was not altered by age. These results indicate that aging may play a significant role in the efficacy of chemoprevention of colon cancer by curcumin. Potential mechanisms responsible for these observations are currently under investigation in our laboratory. [Supported by the American Institute for Cancer Research.]