Identification of inflammation-associated serum and colon markers as indicators of nutritional attenuation of colon carcinogenesis in AOM-induced ob/ob mice consuming dietary navy beans and their fractions Free

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Background: There exists a great need for the identification of non-invasive biomarkers that can be utilized for early detection of colorectal cancer. Epidemiological studies have suggested that increased intake of bioactive food components is associated with decreased colorectal cancer risk. We have previously shown that dietary navy beans and their fractions attenuate colon carcinogenesis in 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. Methods: Ob/Ob mice (n=160) were injected twice with the colon carcinogen azoxymethane and were then randomly placed on 1 of 4 diets: control, whole navy bean, bean residue fraction, or bean extract fraction for up to 40 weeks. A multiplex-based analysis of 15 inflammation and obesity-related serum proteins was conducted. In addition, 84 Th1 Th2 Th3 inflammation-associated gene transcripts were detected via real-time qPCR. Results: Overall, bean fed mice had lower serum levels of the pro-inflammatory cytokine IL-6 and the obesity-related protein leptin and higher levels of the inflammatory cytokine MCP-1 compared to mice on the control diet. Serum levels of IL-4, IL-5, IL-6, IL-10, IFNg, GM-CSF, and Leptin were transiently increased during early stages of colon carcinogenesis. Serum levels of IL-4, IL-5, IL-10, IFNg and GM-CSF were lower in tumor-bearing mice compared to mice with early stage lesions. Analysis of Th1 Th2 Th3 inflammation-associated gene transcripts in colon mucosa samples revealed that mice on bean-based diets showed downregulation (Tnfrsfr8) and upregulation (Cd4, Ccl5, Ptprc, Maf, IL-1r1) of inflammation-related genes. A Cd4 transcript change was seen with both whole bean and residue fraction indicating that a residue-associated compound may contribute to the Cd4 change seen with whole beans. A Tnfrsfr8 transcript change was seen with residue and extract fractions indicating that different compounds in residue and extract may target the same transcript. Conclusion: Changes in serum protein levels of inflammation-related cytokines may serve as reliable indicators of nutritional attenuation. Gene expression changes in colon mucosa may also be indicative of nutritional attenuation. Serum proteins and transcripts identified as altered by a bean-based dietary intervention have potential to serve as biomarkers of colon cancer risk as well as response indicators.