title: Soy Protein Isolate Protects Against Ethanol-Mediated Tumor Progression in Diethylnitrosamine-Treated Male Mice.
abstract: In this study, diethylnitrosamine-treated male mice were assigned to three groups: (i) a 35% high fat ethanol liquid diet (EtOH) with casein as the protein source, (ii) the same EtOH liquid diet with soy protein isolate as the sole protein source (EtOH/SPI), (iii) and a chow group. EtOH feeding continued for 16 weeks. As expected, EtOH increased the incidence and multiplicity of basophilic lesions and adenomas compared with the chow group, P < 0.05. Soy protein replacement of casein in the EtOH diet significantly reduced adenoma progression when compared with the EtOH and EtOH/SPI group (P < 0.05). Tumor reduction in the EtOH/SPI group corresponded to reduced liver injury associated with decreased hepatic Tnfα and Cd14 antigen (Cd14) expression and decreased nuclear accumulation of NF-κB1 protein compared with the EtOH group (P < 0.05). Detection of sphingolipids using high-resolution matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging mass spectrometry revealed increased accumulation of long acyl chain ceramide species, and sphingosine-1-phosphate (S1P) in the EtOH group that were significantly reduced in the EtOH/SPI group. Chronic EtOH feeding also increased mRNA expression of β-catenin transcriptional targets, including cyclin D1 (Ccnd1), matrix metallopeptidase 7 (Mmp7), and glutamine synthetase (Glns), which were reduced in the EtOH/SPI group (P < 0.05). We conclude that soy prevents tumorigenesis by reducing proinflammatory and oxidative environment resulting from EtOH-induced hepatic injury, and by reducing hepatocyte proliferation through inhibition of β-catenin signaling. These mechanisms may involve changes in sphingolipid signaling. Cancer Prev Res; 9(6); 466-75. ©2016 AACR.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas. Arkansas Children's Nutrition Center, Little Rock, Arkansas. mronis@lsuhsc.edu kmercer@uams.edu.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Mercer
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, Arkansas.
authors.forename: Casey
authors.initials: C
authors.lastname: Pulliam
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Leah
authors.initials: L
authors.lastname: Hennings
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Keith
authors.initials: K
authors.lastname: Lai
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, Arkansas.
authors.forename: Mario
authors.initials: M
authors.lastname: Cleves
authors.affiliation: Medical University of South Carolina Proteomic Center, Charleston, South Carolina.
authors.forename: Ellen
authors.initials: E
authors.lastname: Jones
authors.affiliation: Medical University of South Carolina Proteomic Center, Charleston, South Carolina.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Drake
authors.affiliation: Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana. mronis@lsuhsc.edu kmercer@uams.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Ronis
mesh_terms: D000236:Adenoma / Q000139:chemically induced / Q000473:pathology*; D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D004032:Diet; D004052:Diethylnitrosamine / Q000633:toxicity; D018450:Disease Progression; D000431:Ethanol / Q000633:toxicity; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D030262:Soybean Proteins / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000477:Alkylating Agents; D030262:Soybean Proteins; D004052:Diethylnitrosamine; D000431:Ethanol