Microarray Analyses of Genes Differentially Expressed by Diet (Black Beans and Soy Flour) during Azoxymethane-Induced Colon Carcinogenesis in Rats

Abstract

We previously demonstrated that black bean (BB) and soy flour (SF)-based diets inhibit azoxymethane (AOM)-induced colon cancer. The objective of this study was to identify genes altered by carcinogen treatment in normal-appearing colonic mucosa and those attenuated by bean feeding. Ninety-five male F344 rats were fed control (AIN) diets upon arrival. At 4 and 5 weeks, rats were injected with AOM (15 mg/kg) or saline and one week later administered an AIN, BB-, or SF-based diet. Rats were sacrificed after 31 weeks, and microarrays were conducted on RNA isolated from the distal colonic mucosa. AOM treatment induced a number of genes involved in immunity, including several MHC II-associated antigens and innate defense genes (RatNP-3, Lyz2, Pla2g2a). BB- and SF-fed rats exhibited a higher expression of genes involved in energy metabolism and water and sodium absorption and lower expression of innate (RatNP-3, Pla2g2a, Tlr4, Dmbt1) and cell cycle-associated (Cdc2, Ccnb1, Top2a) genes. Genes involved in the extracellular matrix (Col1a1, Fn1) and innate immunity (RatNP-3, Pla2g2a) were induced by AOM in all diets, but to a lower extent in bean-fed animals. This profile suggests beans inhibit colon carcinogenesis by modulating cellular kinetics and reducing inflammation, potentially by preserving mucosal barrier function.

Dmbt1 does not affect a Western style diet-induced liver damage in mice

“…The study was also warranted based on results from several in vivo studies suggesting that there is a diet-dependent up or down regulation of Dmbt1/dmbt1 in the liver and parts of the gut. (18–20) Further, DMBT1 has been linked to liver injury and repair mechanisms concerning liver disease. (16,17) …”

“…(14) Furthermore, data from animal models indicate that there is a diet-dependent up or down regulation of the Dmbt1/dmbt1 expression in the liver and parts of the gut. (18–20) Starting from this background the purpose of the present study was to investigate if Dmbt1 affects a Western style diet-induced liver damage in Dmbt1 knockout mice.…”

Grain Legume Consumption Inhibits Colorectal Tumorigenesis: A Meta-Analysis of Human and Animal Studies

“…As shown in Table 4, 14 animal studies evaluated the effect of grain legume consumption on colorectal tumorigenesis using 253 animals (248 males and five females) on control diets and 355 animals (350 males and five females) on 19 different grain-legume-containing diets [78][79][80][81][82][83][84][85][86][87][88][89]. Eight diets contained whole dry beans, seven contained dry bean fractions (three fiber factions, three ethanol extract, and one ethanol extract residue); two diets each contained lentils or chickpeas, and one diet each contained black-eyed peas or dry peas.…”

“…The animal studies have limitations: first, in four of the seven tumor endpoint studies, grain legumes made up the majority of the diet (45-75%; Table 4) [78][79][80]82], concentrations that are not relevant for human consumption. However, three studies showed a protective effect of the ethanol extract of navy beans fed at 10% of the diet (Table 4); the 2015 U.S. dietary guidelines for legume consumption are equivalent to ~2-5% of the diet [76], concentrations that should be evaluated in future animal studies.…”

“…Second, grain legumes can inhibit survival of neoplastic colorectal epithelial cells by attenuating the NF-kB pathway [163][164][165]. Third, grain legumes can decrease proliferation of neoplastic colorectal epithelial cells [156,163] by inducing genes that promote cell cycle arrest in G1/S and G2/M phases through p53-mediated pathways [82,156,165]. Fourth, grain legumes can inhibit survival and proliferation of neoplastic cells by suppressing the Akt (protein kinase B)/mTOR (mammalian target of rapamycin) pathway and upregulating the AMPK pathway, as shown for mammary carcinomas [166,167].…”