title: Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.
abstract: Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein source on hepatic tumor promotion in a mouse model reflecting aspects of non-alcoholic fatty liver disease (NAFLD). A high-fat liquid diet with casein as the protein source promotes hepatic injury and tumor promotion in diethylnitrosamine-treated mice. Replacing casein with a soy protein isolate led to a pronounced diminishment of tumor promotion and associated hepatic injury and inflammation. The study thus demonstrates that a dietary protein source can have beneficial, preventative effects on hepatic tumor promotion.
authors.affiliation: 1 Department of Pediatrics at the University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.|2 Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Mercer
authors.affiliation: 3 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Casey F
authors.initials: CF
authors.lastname: Pulliam
authors.affiliation: 3 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Kim B
authors.initials: KB
authors.lastname: Pedersen
authors.affiliation: 4 Department of Pathology at the University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Hennings
authors.affiliation: 3 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Martin Jj
authors.initials: MJ
authors.lastname: Ronis
mesh_terms: D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000473:pathology; D030262:Soybean Proteins / Q000627:therapeutic use*
chemical_list: D030262:Soybean Proteins
keywords: Tumor promotion; casein; high fat feeding; liver cancer; non-alcoholic fatty liver disease; soy protein