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Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.
Exp Biol Med (Maywood) 2017; 242(6):635-644EB

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+Show Affiliations

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.3 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.3 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.4 Department of Pathology at the University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.3 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28056552

Citation

Mercer, Kelly E., et al. "Soy Protein Isolate Inhibits Hepatic Tumor Promotion in Mice Fed a High-fat Liquid Diet." Experimental Biology and Medicine (Maywood, N.J.), vol. 242, no. 6, 2017, pp. 635-644.
Mercer KE, Pulliam CF, Pedersen KB, et al. Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet. Exp Biol Med (Maywood). 2017;242(6):635-644.
Mercer, K. E., Pulliam, C. F., Pedersen, K. B., Hennings, L., & Ronis, M. J. (2017). Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet. Experimental Biology and Medicine (Maywood, N.J.), 242(6), pp. 635-644. doi:10.1177/1535370216685436.
Mercer KE, et al. Soy Protein Isolate Inhibits Hepatic Tumor Promotion in Mice Fed a High-fat Liquid Diet. Exp Biol Med (Maywood). 2017;242(6):635-644. PubMed PMID: 28056552.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet. AU - Mercer,Kelly E, AU - Pulliam,Casey F, AU - Pedersen,Kim B, AU - Hennings,Leah, AU - Ronis,Martin Jj, Y1 - 2017/01/05/ PY - 2017/1/7/pubmed PY - 2017/6/20/medline PY - 2017/1/7/entrez KW - Tumor promotion KW - casein KW - high fat feeding KW - liver cancer KW - non-alcoholic fatty liver disease KW - soy protein SP - 635 EP - 644 JF - Experimental biology and medicine (Maywood, N.J.) JO - Exp. Biol. Med. (Maywood) VL - 242 IS - 6 N2 - 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. SN - 1535-3699 UR - https://www.unboundmedicine.com/medline/citation/28056552/Soy_protein_isolate_inhibits_hepatic_tumor_promotion_in_mice_fed_a_high_fat_liquid_diet_ L2 - http://journals.sagepub.com/doi/full/10.1177/1535370216685436?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -