Based on the protective effects of cooked dry bean consumption in a human intervention study, we evaluated which fraction of cooked dry beans is responsible for its cancer-preventive effects. Cooked navy beans (whole beans), the insoluble fraction (bean residue) or soluble fraction of the 60% (vol:vol) ethanol extract of cooked navy beans (bean extract), or a modified AIN-93G diet (16.6% fat including 12.9% lard) as control diet were fed to 160 male obese ob/ob mice after 2 azoxymethane injections. In comparison to control-fed mice, dysplasia, adenomas, or adenocarcinomas were detected in fewer mice on either bean fraction diet (percent reduction from control: whole beans 54%, P = 0.10; bean residue 81%, P = 0.003 ; bean extract 91%, P = 0.007) , and any type of colon lesions, including focal hyperplasia, were found in fewer mice on each of the 3 bean diets percent reduction from control: whole bean 56%, P = 0.04; bean residue 67%, P = 0.01; bean extract 87%, P = 0.0003. These results suggest that both the soluble and the insoluble fraction of the extract contribute to the cancer-protective effect of cooked navy beans.

Although inflammatory cytokines and obesity-associated serum proteins have been reported as biomarkers of colorectal adenoma risk in humans, little is known of biomarkers of response to interventions that attenuate tumorigenesis. Dietary navy beans and their fractions attenuate colon carcinogenesis in carcinogen-induced genetically obese mice. We hypothesized that this attenuation would be associated with changes in inflammatory cytokines and obesity-related serum proteins that may serve as measures of efficacy. ob/ob mice (n = 160) were injected with the carcinogen azoxymethane (AOM) to induce colon cancer and randomly placed on one of four diets (control, whole navy bean, bean residue fraction, or bean extract fraction) for 26 to 28 wk. Serum was analyzed for 14 inflammationor obesity-related proteins, and colon RNA was analyzed for expression of 84 inflammationassociated genes. Six of 14 serum proteins were increased [i.e., interleukin (IL)-4, IL-5, IL-6, IL-10, IFNγ, granulocyte macrophage colony-stimulating factor] in hyperplastic/dysplastic stages of colon carcinogenesis. Bean-fed mice had significantly higher monocyte chemoattractant protein-1 and lower IL-6 levels in serum. In colon mucosa, 55 of 84 inflammationassociated genes differed between AOM-induced and noninduced mice. Of the 55 AOM-induced genes, 5 were counteracted by bean diets, including IL-6 whose increase in expression levels was attenuated by bean diets in AOM-induced mice. In summary, IL-6 emerged as a serum protein that was increased in hyperplastic/dysplastic stages of colon carcinogenesis, but attenuated with bean-based diet in serum and colon mucosa. Changes in a subset of inflammation-associated serum proteins and colon gene expression may serve as response indicators of dietary attenuation of colon carcinogenesis.

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