Dietary cooked navy beans and their fractions attenuate colon carcinogenesis in azoxymethane-induced ob/ob mice

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%, 373 374 G. BOBE ET AL. 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. INTRODUCTION Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer and the fourth most common cause of cancer-related death worldwide (1). In the United States, CRC is the fourth leading cancer in incidence rates and the second leading cause of cancer-related mortality with a 5-yr survival rate of 64% (2). Despite the effectiveness of screening (3,4), there is limited impact for CRC prevention because of low screening rates (5). Nutrition remains critical for CRC prevention. It is estimated that nutrition could prevent 70-80% of all CRC cases (6). This is important, as the annual CRC treatment costs in the United States are estimated to be $6.5 billion (7). Two of the main risk factors for CRC, which are both diet related, are obesity and inflammation (8). Thus, ob/ob mice might provide a suitable animal model to study the link between diet and CRC because they have a mutation in the leptin gene, which results in hyperphagia, obesity, hyperinsulinemia, hyperglycemia, and increased inflammatory response to liposaccharides (9). Dry beans (Phaseolus vulgaris L.), which belong to the Leguminosae family, are a dietary staple in many Latin American, Eastern, and South African countries that potentially could prevent CRC (10,11). Ecological analysis indicates a decreased risk of death associated with colon cancer in countries with higher consumption of beans (12). In studies that have examined the association between colon cancer and individual intakes of legumes, the results indicate a protective effect in populations with higher legume consumption (13-18). In the only study that examined the effect of dry bean consumption separately, male participants, who consumed at least 31 g of cooked dry beans daily, had reduced risk of advanced adenomatous polyp recurrence in a 4-yr nutrition intervention study (Polyp Prevention Trial (19); unpublished data). In animal models, dry beans commonly consumed in the United States, such as pinto, black, and navy beans, reduced azoxymethane(AOM)-induced colon adenocarcinomas in F344 rat