NDLI: Dietary soy protein inhibits DNA damage and cell survival of colon epithelial cells through attenuated expression of fatty acid synthase.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Xiao, Rijin Su, Ying Simmen, Rosalia C. M. Simmen, Frank A.
Description	Country affiliation: United States Author Affiliation: Xiao R ( Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.)
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 overexpression characterizes early tumorigenesis. Here, we show that colonic FASN levels are reduced with dietary intake of soy protein isolate (SPI), compared with a control casein diet, in male Sprague-Dawley rats administered the colon carcinogen azoxymethane. SPI consumption resulted in decreased serum insulin levels and decreased azoxymethane-induced tumor suppressor p53 phosphorylation in colon crypt epithelium. To evaluate potential links between insulin and FASN leading to DNA damage, C2(BBe)1 colon epithelial cells, treated with insulin and/or the carcinogen N-nitroso-N-methylurea (NMU), were evaluated for DNA damage and apoptosis after transfection with control or FASN small interfering RNAs (siRNAs). While the numbers of DNA apurinic/apyrimidinic sites (biomarker 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 C2(BBe)1, as well as intestinal epithelial cell (IEC)-6, was enhanced by transfected FASN siRNA. Increased FASN expression in IEC-6 cells by addition of liver X receptor agonist T0901317 did not affect apurinic/apyrimidinic 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.
File Format	HTM / HTML
ISSN	01931857
Issue Number	4
Volume Number	294
Journal	AJP: Gastrointestinal and Liver Physiology
e-ISSN	15221547
Language	English
Publisher	American Physiological Society
Publisher Date	2008-04-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Physiology Discipline Gastroenterology Anticarcinogenic Agents Pharmacology Cell Transformation, Neoplastic Drug Effects Colon Dna Damage Dietary Proteins Epithelial Cells Fatty Acid Synthases Metabolism Soybean Proteins Animals Administration & Dosage Apoptosis Azoxymethane Toxicity Caco-2 Cells Carcinogens Caseins Genetics Pathology Cerulenin Enzymology Down-regulation Fatty Acid Synthase, Type I Fatty Acid Synthesis Inhibitors Female Humans Hydrocarbons, Fluorinated Insulin Blood Male Methylnitrosourea Phosphorylation Rna Interference Rna, Small Interfering Rats Rats, Sprague-dawley Sulfonamides Transfection Tumor Suppressor Protein P53 Journal Article Research Support, N.i.h., Extramural Research Support, U.s. Gov't, Non-p.h.s.
Content Type	Text
Resource Type	Article
Subject	Hepatology Physiology Physiology (medical) Gastroenterology

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