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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #223803
Title: Dietary Soy Protein Inhibits DNA Damage and Cell Survival of Colon Epithelial Cells through Attenuated Expression of Fatty Acid Synthase

Author
item XIAO, RIJIN - ACNC/UAMS
item SU, YING - ACNC/UAMS
item SIMMEN, ROSALIA - ACNC/UAMS
item SIMMEN, FRANK - ACNC/UAMS

Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/28/2008
Publication Date: 4/9/2008
Citation: Xiao, R., Su, Y., Simmen, R.C., Simmen, F.A. 2008. Dietary soy protein inhibits DNA damage and cell survival of colon epithelial cells through attenuated expression of fatty acid synthase. American Journal of Physiology - Gastrointestinal and Liver Physiology. 294(4):G868-G876.

Interpretive Summary: Previous work has suggested that a diet rich in soy protein may protect against development of colo-rectal cancers in humans and rodents. In the present study, we examined if soy protein exerts its colon cancer-inhibitory effects by changing expression of an important enzyme that makes fatty acids (Fatty Acid Synthase). Indeed, we found that soy protein diet reduces the cellular expression of Fatty Acid Synthase and that this leads to increased cell death of colon cells when their DNA becomes damaged by cancer-causing agents. Our study also found that a soy protein diet led to lower blood levels of insulin, and we showed that this also contributes to the cancer-protective effect. Overall, our study has led to a new paradigm for explaining how diet affects cancer development in rodents, and with implications for humans.

Technical Abstract: Dietary intake of soy protein decreases tumor incidence in rat models of chemically induced colon cancer. We hypothesized that decreased expression of Fatty Acid Synthase (FASN) underlies, in part, the tumor preventive effects of soy protein, since FASN over-expression characterizes early tumorigenesis. Here, we show that colonic FASN levels are reduced with dietary intake of Soy Protein Isolate (SPI), compared to control Casein (CAS) diet, in male Sprague-Dawley rats administered the colon carcinogen azoxymethane (AOM). SPI consumption resulted in decreased serum insulin levels and decreased AOM-induced tumor suppressor p53 phosphorylation in colon crypt epithelium. To evaluate potential links between insulin and FASN leading to DNA damage, C2BBe1 colon epithelial cells, treated with insulin and/or the carcinogen NMU were evaluated for DNA damage and apoptosis after transfection with control or FASN siRNAs. While the numbers of DNA apurinic/apyrimidinic (AP) sites (bio-marker of DNA damage) induced by NMU were unaffected by transfection of FASN siRNA, insulin induction of these sites was decreased with FASN knockdown. By contrast, NMU-induced apoptosis of C2BBe1, as well as intestinal epithelial IEC-6 cells, was enhanced by transfected FASN siRNA. Increased FASN expression in IEC-6 cells by addition of LXR agonist T0901317 did not affect AP site number but enhanced cell killing by cerulenin, a FASN inhibitor. Moreover, insulin rescued NMU-treated cells from apoptosis in an FASN-dependent manner. Results suggest that dietary SPI, by decreasing circulating insulin levels and colon FASN expression, attenuates insulin-induced DNA damage and FASN-mediated anti-apoptosis during carcinogenesis, resulting in an overall reduced tumorigenic state.