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Elisia I, Yeung M, Kowalski S, Wong A, Dietrich C, Wu S, Chang V, Adomat H, Krystal G. Saponins in soy reduce NNK-induced lung cancer by increasing plasma isoflavone levels. Sci Rep 2025; 15:12714. [PMID: 40223151 PMCID: PMC11994769 DOI: 10.1038/s41598-025-97687-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 04/07/2025] [Indexed: 04/15/2025] Open
Abstract
Recently, we found, using a cigarette carcinogen-induced lung cancer model, that soy protein isolate (SPI) was superior to casein in preventing lung cancer. In this study, we have attempted to identify the component(s) within SPI responsible for this chemopreventive effect. We fractionated the SPI using ethanol to separate the ethanol-soluble fraction (ESF) and the washed SPI and compared their efficacy to diets made with amino acids that comprise soy protein or casein, in preventing lung tumor formation in A/J mice. Only the ethanol-soluble fraction was as effective as SPI in preventing lung tumor formation. Since isoflavones and saponins are known ethanol-soluble bioactives from soy, we added isoflavones, or saponins or both to casein and found that isoflavones or saponins alone did not reduce lung nodule formation. However, when we combined soy saponins and isoflavones, we saw a significant (P < 0.05) reduction in NNK-induced lung nodules, and an increase in plasma isoflavone levels, suggesting that the saponins may enhance the bioavailability of the isoflavones in these mice. Taken together, we suggest that the superior efficacy of SPI over casein could be attributed, at least in part, to the synergistic effect of the soy saponins and isoflavones.
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Affiliation(s)
- Ingrid Elisia
- The Terry Fox Laboratory, Pathology & Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia, 675 West 10th Avenue, Vancouver, BC, V5L 1Z3, Canada
| | - Michelle Yeung
- The Terry Fox Laboratory, Pathology & Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia, 675 West 10th Avenue, Vancouver, BC, V5L 1Z3, Canada
| | - Sara Kowalski
- The Terry Fox Laboratory, Pathology & Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia, 675 West 10th Avenue, Vancouver, BC, V5L 1Z3, Canada
| | - Amy Wong
- The Terry Fox Laboratory, Pathology & Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia, 675 West 10th Avenue, Vancouver, BC, V5L 1Z3, Canada
| | - Colton Dietrich
- The Terry Fox Laboratory, Pathology & Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia, 675 West 10th Avenue, Vancouver, BC, V5L 1Z3, Canada
| | - Samantha Wu
- The Terry Fox Laboratory, Pathology & Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia, 675 West 10th Avenue, Vancouver, BC, V5L 1Z3, Canada
| | - Vianne Chang
- The Terry Fox Laboratory, Pathology & Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia, 675 West 10th Avenue, Vancouver, BC, V5L 1Z3, Canada
| | - Hans Adomat
- The Vancouver Prostate Centre at Vancouver General Hospital, Vancouver, BC, Canada
| | - Gerald Krystal
- The Terry Fox Laboratory, Pathology & Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia, 675 West 10th Avenue, Vancouver, BC, V5L 1Z3, Canada.
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Zhang CY, Liu S, Yang M. Antioxidant and anti-inflammatory agents in chronic liver diseases: Molecular mechanisms and therapy. World J Hepatol 2023; 15:180-200. [PMID: 36926234 PMCID: PMC10011909 DOI: 10.4254/wjh.v15.i2.180] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 11/30/2022] [Accepted: 02/07/2023] [Indexed: 02/24/2023] Open
Abstract
Chronic liver disease (CLD) is a continuous process that causes a reduction of liver function lasting more than six months. CLD includes alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), chronic viral infection, and autoimmune hepatitis, which can lead to liver fibrosis, cirrhosis, and cancer. Liver inflammation and oxidative stress are commonly associated with the development and progression of CLD. Molecular signaling pathways such as AMP-activated protein kinase (AMPK), C-Jun N-terminal kinase, and peroxisome proliferator-activated receptors (PPARs) are implicated in the pathogenesis of CLD. Therefore, antioxidant and anti-inflammatory agents from natural products are new potent therapies for ALD, NAFLD, and hepatocellular carcinoma (HCC). In this review, we summarize some powerful products that can be potential applied in all the stages of CLD, from ALD/NAFLD to HCC. The selected agents such as β-sitosterol, curcumin, genistein, and silymarin can regulate the activation of several important molecules, including AMPK, Farnesoid X receptor, nuclear factor erythroid 2-related factor-2, PPARs, phosphatidylinositol-3-kinase, and lysyl oxidase-like proteins. In addition, clinical trials are undergoing to evaluate their efficacy and safety.
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Affiliation(s)
- Chun-Ye Zhang
- Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, United States
| | - Shuai Liu
- The First Affiliated Hospital, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65211, United States.
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Kusumah J, Gonzalez de Mejia E. Impact of soybean bioactive compounds as response to diet-induced chronic inflammation: A systematic review. Food Res Int 2022; 162:111928. [DOI: 10.1016/j.foodres.2022.111928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 09/07/2022] [Accepted: 09/08/2022] [Indexed: 11/04/2022]
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Dia VP. Plant sources of bioactive peptides. BIOLOGICALLY ACTIVE PEPTIDES 2021:357-402. [DOI: 10.1016/b978-0-12-821389-6.00003-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Jeminiwa BO, Knight RM, Braden TD, Cruz-Espindola C, Boothe DM, Akingbemi BT. Regulation of the neuroendocrine axis in male rats by soy-based diets is independent of age and due specifically to isoflavone action†. Biol Reprod 2020; 103:892-906. [PMID: 32520353 DOI: 10.1093/biolre/ioaa101] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 05/28/2020] [Accepted: 06/05/2020] [Indexed: 11/13/2022] Open
Abstract
Soy-based foods are consumed for their health beneficial effects, implying that the population is exposed to soy isoflavones in the diet. Herein, male rats at 21, 35, and 75 days of age were maintained either on a casein control diet, soybean meal (SBM), or control diet supplemented with daidzin and genistin (G + D) for 14 days. Feeding of SBM and G + D diets decreased testicular testosterone (T) secretion regardless of age. Altered androgen secretion was due to decreased (P < 0.05) Star and Hsd17β protein in the testes and was associated with increased (P < 0.05) Lhβ and Fshβ subunit protein expression in pituitary glands. Second, male rats were fed either a casein control diet, control diet + daidzin, control diet + genistin, or control diet + genistin + daidzin (G + D). Compared to control, feeding of all isoflavone-containing diets decreased (P < 0.05) testicular T concentrations, and more so in the G + D diet group. Interestingly, Esr1 and androgen receptor protein and pituitary Fshβ with Lhβ subunit protein were increased (P < 0.05) by feeding of genistin and G + D diets, but not the daidzin diet. However, daidzein and genistein both caused a concentration dependent inhibition (P < 0.05) of T secretion by Leydig cells in vitro with IC50 of 184 ηM and 36 ηM, respectively. Results demonstrated that altered testicular steroidogenic capacity and pituitary FSHβ and LHβ subunit expression due to soy-based diets result from specific actions by genistein and daidzein. Experiments to assess effects of isoflavone regulation of intratesticular androgen concentrations on male fertility are warranted.
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Affiliation(s)
- Bamidele O Jeminiwa
- Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
| | - Rachel M Knight
- Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
| | - Tim D Braden
- Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
| | - Crisanta Cruz-Espindola
- Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
| | - Dawn M Boothe
- Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
| | - Benson T Akingbemi
- Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
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Ronis MJ, Mercer KE, Shankar K, Pulliam C, Pedersen K, Ingelman-Sundberg M, Friso S, Samuelson D, Del Valle L, Taylor C, Welsh DA. Potential role of gut microbiota, the proto-oncogene PIKE (Agap2) and cytochrome P450 CYP2W1 in promotion of liver cancer by alcoholic and nonalcoholic fatty liver disease and protection by dietary soy protein. Chem Biol Interact 2020; 325:109131. [PMID: 32417163 DOI: 10.1016/j.cbi.2020.109131] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 05/06/2020] [Indexed: 12/12/2022]
Abstract
We have previously demonstrated promotion of diethylnitrosamine (DEN) initiated liver tumorigenesis after feeding diets high in fat or ethanol (EtOH) to male mice. This was accompanied by hepatic induction of the proto-oncogene PIKE (Agap2). Switch of dietary protein from casein to soy protein isolate (SPI) significantly reduced tumor formation in these models. We have linked EtOH consumption in mice to microbial dysbiosis. Adoptive transfer studies demonstrate that microbiota from mice fed ethanol can induce hepatic steatosis in the absence of ethanol suggesting that microbiota or the microbial metabolome play key roles in development of fatty liver disease. Feeding SPI significantly changed gut bacteria in mice increasing alpha diversity (P < 0.05) and levels of Clostidiales spp. Feeding soy formula to piglets also resulted in significant changes in microbiota, the pattern of bile acid metabolites and in inhibition of the intestinal-hepatic FXR/FGF19-SHP pathway which has been linked to both steatosis and hepatocyte proliferation. Moreover, feeding SPI also resulted in induction of hepatic PPARα signaling and inhibition of PIKE mRNA expression coincident with inhibition of steatosis and cancer prevention. Feeding studies in the DEN model with differing dietary fats demonstrated tumor promotion specific to the saturated fat, cocoa butter relative to diets containing olive oil or corn oil associated with microbial dysbiosis including dramatic increases in Lachnospiraceae particularly from the genus Coprococcus. Immunohistochemical analysis demonstrated that tumors from EtOH-fed mice and patients with alcohol-associated HCC also expressed high levels of a novel cytochrome P450 enzyme CYP2W1. Additional adoptive transfer experiments and studies in knockout mice are required to determine the exact relationship between soy effects on the microbiota, expression of PIKE, CYP2W1, PPARα activation and prevention of tumorigenesis.
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Affiliation(s)
- Martin J Ronis
- Louisiana State University Health Sciences Center, New Orleans, USA.
| | | | | | - Casey Pulliam
- Louisiana State University Health Sciences Center, New Orleans, USA
| | - Kim Pedersen
- Louisiana State University Health Sciences Center, New Orleans, USA
| | | | | | | | - Luis Del Valle
- Louisiana State University Health Sciences Center, New Orleans, USA
| | - Chris Taylor
- Louisiana State University Health Sciences Center, New Orleans, USA
| | - David A Welsh
- Louisiana State University Health Sciences Center, New Orleans, USA
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Barron KA, Jeffries KA, Krupenko NI. Sphingolipids and the link between alcohol and cancer. Chem Biol Interact 2020; 322:109058. [PMID: 32171848 DOI: 10.1016/j.cbi.2020.109058] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 11/20/2019] [Accepted: 03/10/2020] [Indexed: 02/07/2023]
Abstract
Epidemiological evidence underscores alcohol consumption as a strong risk factor for multiple cancer types, with liver cancer being most commonly associated with alcohol intake. While mechanisms linking alcohol consumption to malignant tumor development are not fully understood, the likely players in ethanol-induced carcinogenesis are genotoxic stress caused by formation of acetaldehyde, increased oxidative stress, and altered nutrient metabolism, including the impairment of methyl transfer reactions. Alterations of sphingolipid metabolism and associated signaling pathways are another potential link between ethanol and cancer development. In particular, ceramides are involved in the regulation of cellular proliferation, differentiation, senescence, and apoptosis and are known to function as important regulators of malignant transformation as well as tumor progression. However, to date, the cross-talk between ceramides and alcohol in cancer disease is largely an open question and only limited data are available on this subject. Most studies linking ceramide to cancer considered liver steatosis as the underlying mechanism, which is not surprising taking into consideration that ceramide pathways are an integral part of the overall lipid metabolism. This review summarizes the latest studies pointing to ceramide as an important mediator of cancer-promoting effects of chronic alcohol consumption and underscores the necessity of understanding the role of sphingolipids and lipid signaling in response to alcohol in order to prevent and/or successfully manage diseases caused by alcohol.
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Affiliation(s)
| | | | - Natalia I Krupenko
- Department of Nutrition, UNC Chapel Hill, USA; Nutrition Research Institute, UNC Chapel Hill, USA.
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Hu S, Li SW, Yan Q, Hu XP, Li LY, Zhou H, Pan LX, Li J, Shen CP, Xu T. Natural products, extracts and formulations comprehensive therapy for the improvement of motor function in alcoholic liver disease. Pharmacol Res 2019; 150:104501. [PMID: 31689520 DOI: 10.1016/j.phrs.2019.104501] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 10/08/2019] [Accepted: 10/15/2019] [Indexed: 02/07/2023]
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Song BJ, Abdelmegeed MA, Cho YE, Akbar M, Rhim JS, Song MK, Hardwick JP. Contributing Roles of CYP2E1 and Other Cytochrome P450 Isoforms in Alcohol-Related Tissue Injury and Carcinogenesis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1164:73-87. [PMID: 31576541 DOI: 10.1007/978-3-030-22254-3_6] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The purpose of this review is to briefly summarize the roles of alcohol (ethanol) and related compounds in promoting cancer and inflammatory injury in many tissues. Long-term chronic heavy alcohol exposure is known to increase the chances of inflammation, oxidative DNA damage, and cancer development in many organs. The rates of alcohol-mediated organ damage and cancer risks are significantly elevated in the presence of co-morbidity factors such as poor nutrition, unhealthy diets, smoking, infection with bacteria or viruses, and exposure to pro-carcinogens. Chronic ingestion of alcohol and its metabolite acetaldehyde may initiate and/or promote the development of cancer in the liver, oral cavity, esophagus, stomach, gastrointestinal tract, pancreas, prostate, and female breast. In this chapter, we summarize the important roles of ethanol/acetaldehyde in promoting inflammatory injury and carcinogenesis in several tissues. We also review the updated roles of the ethanol-inducible cytochrome P450-2E1 (CYP2E1) and other cytochrome P450 isozymes in the metabolism of various potentially toxic substrates, and consequent toxicities, including carcinogenesis in different tissues. We also briefly describe the potential implications of endogenous ethanol produced by gut bacteria, as frequently observed in the experimental models and patients of nonalcoholic fatty liver disease, in promoting DNA mutation and cancer development in the liver and other tissues, including the gastrointestinal tract.
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Affiliation(s)
- Byoung-Joon Song
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
| | - Mohamed A Abdelmegeed
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA
| | - Young-Eun Cho
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.,Department of Food Science and Nutrition, Andong National University, Andong, Republic of Korea
| | - Mohammed Akbar
- Division of Neuroscience and Behavior, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA
| | - Johng S Rhim
- Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Min-Kyung Song
- Investigational Drug Branch, National Cancer Institute, NIH, Bethesda, MD, USA
| | - James P Hardwick
- Biochemistry and Molecular Pathology in the Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA
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Mercer KE, Pulliam CF, Pedersen KB, Hennings L, Ronis MJ. Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet. Exp Biol Med (Maywood) 2017; 242:635-644. [PMID: 28056552 DOI: 10.1177/1535370216685436] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
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.
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Affiliation(s)
- Kelly E Mercer
- 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
| | - Casey F Pulliam
- 3 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
| | - Kim B Pedersen
- 3 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
| | - Leah Hennings
- 4 Department of Pathology at the University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Martin Jj Ronis
- 3 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
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Mercer KE, Pulliam C, Hennings L, Lai K, Cleves M, Jones E, Drake RR, Ronis M. Soy Protein Isolate Protects Against Ethanol-Mediated Tumor Progression in Diethylnitrosamine-Treated Male Mice. Cancer Prev Res (Phila) 2016; 9:466-75. [PMID: 27006377 DOI: 10.1158/1940-6207.capr-15-0417] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2015] [Accepted: 03/02/2016] [Indexed: 12/16/2022]
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.
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Affiliation(s)
- Kelly E Mercer
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas. Arkansas Children's Nutrition Center, Little Rock, Arkansas.
| | - Casey Pulliam
- Arkansas Children's Nutrition Center, Little Rock, Arkansas
| | - Leah Hennings
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Keith Lai
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Mario Cleves
- Arkansas Children's Nutrition Center, Little Rock, Arkansas
| | - Ellen Jones
- Medical University of South Carolina Proteomic Center, Charleston, South Carolina
| | - Richard R Drake
- Medical University of South Carolina Proteomic Center, Charleston, South Carolina
| | - Martin Ronis
- Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
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