Select dietary fats and fibers block carcinogen-induced down-regulation down-regulation of colonic protein kinase C.
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abstract
We have previously demonstrated that diet alters protein kinase C (PKC) mediated signal transduction in the colon. In order to further understand the mechanisms by which diet alters colon cancer risk, the effect of different fats and fibers on colonie PKC a, 8 and expression in the rat experimental colon carcinogenesis model was investigated. In a 2 2 2 factorial design, groups of 20 male Sprague-Dawley rats (one week post-weaning) were fed diets containing either 15% (w/w) corn oil or fish oil and either 6% (w/w) cellulose or pectin throughout the study. At 5 and 6 weeks of age, rats were injected s.c. with either azoxymethane (AOM) or saline. At 18 and 35 weeks post injection, the steady-state levels of colonie mRNA and protein for PKC , and . the major protein kinase isoforms in rat colon, were determined using quantitative polymerase chain reaction and immunoblotting, respectively. In general, PKC , and mRNA levels were not affected by diets or AOM. However, there was a major suppressive effect of carcinogen on PKC , and protein levels at both time points (P<0.05). A time dependent epigenetic effect of diet on PKC and levels was observed with fish oil reversing the suppressive effect of carcinogen at the first time point compared to corn oil, and pectin reversing this effect at the second time point compared to cellulose. These data support the hypothesis that certain dietary fats and fibers may be protective against the development of colon cancer through alteration of PKC signaling pathways in a time dependent manner. Supported by NIH CA59034 and CA61750.
