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Alcohol and Cancer pp 115–126Cite as

Diet Supplementation with Soy Protein Isolate, but Not the Isoflavone Genistein, Protects Against Alcohol-Induced Tumor Progression in DEN-Treated Male Mice

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1032))

Abstract

Diethylnitrosamine-treated male mice were assigned to 4 groups: a casein-based 35% high fat ethanol liquid diet (EtOH), an EtOH diet made with soy protein isolate protein (EtOH/SOY), an EtOH liquid diet supplemented with genistein (EtOH/GEN) and a chow group. EtOH feeding, final concentration 5% (v/v), continued for 16 wks. EtOH increased incidence and multiplicity of basophilic lesions and adenomas compared to the chow group, (p < 0.05). The EtOH/SOY group had reduced adenoma progression when compared to the EtOH and EtOH/GEN group, (p < 0.05). Genistein supplementation had no protective effect. Soy feeding significantly reduced serum ALT concentrations (p < 0.05), decreased hepatic TNFα and CD-14 expression and decreased nuclear accumulation of NFκB protein in EtOH/SOY-treated mice compared to the EtOH group (p < 0.05). With respect to ceramides, high resolution MALDI-FTICR Imaging mass spectrometry revealed changes in the accumulation of long acyl chain ceramide species, in particular C18, in the EtOH group when compared to the EtOH/SOY group. Additionally, expression of acid ceramidase and sphingosine kinase 1 which degrade ceramide into sphingosine and convert sphingosine to sphingosine-1-phosphate (S1P) respectively and expression of S1P receptors S1PR2 and S1PR3 were all upregulated by EtOH and suppressed in the EtOH/SOY group, p < 0.05. EtOH feeding also increased hepatocyte proliferation and mRNA expression of β-catenin targets, including cyclin D1, MMP7 and glutamine synthase, which were reduced in the EtOH/SOY group, p < 0.05. These findings suggest that soy prevents tumorigenesis by reducing inflammation and by reducing hepatocyte proliferation through inhibition of EtOH-mediated β-catenin signaling. These mechanisms may involve blockade of sphingolipid signaling.

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Acknowledgements

These studies were funded in part by NCI R21 CA169389 (M.J.R.) and the Lyon Foundation (K.E.M.).

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Authors and Affiliations

  1. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    K. E. Mercer & M. A. Cleves

  2. Arkansas Children’s Nutrition Center, Little Rock, AR, USA

    K. E. Mercer & M. A. Cleves

  3. Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    C. F. Pulliam & M. J. J. Ronis

  4. Departmant of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    L. Hennings

  5. Medical University of South Carolina Proteomic Center, Charleston, SC, USA

    E. E. Jones & R. R. Drake

Authors
  1. K. E. Mercer
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  2. C. F. Pulliam
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  3. L. Hennings
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  4. M. A. Cleves
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  5. E. E. Jones
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  6. R. R. Drake
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  7. M. J. J. Ronis
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Corresponding author

Correspondence to M. J. J. Ronis .

Editor information

Editors and Affiliations

  1. Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA

    Vasilis Vasiliou

  2. Distilled Spirits Council of the US, Washington, DC, USA

    Samir Zakhari

  3. Mishra Laboratory, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Lopa Mishra

  4. Salem Medical Centre, University of Heidelberg, Heidelberg, Baden-Württemberg, Germany

    Helmut K. Seitz

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Mercer, K.E. et al. (2018). Diet Supplementation with Soy Protein Isolate, but Not the Isoflavone Genistein, Protects Against Alcohol-Induced Tumor Progression in DEN-Treated Male Mice. In: Vasiliou, V., Zakhari, S., Mishra, L., Seitz, H. (eds) Alcohol and Cancer. Advances in Experimental Medicine and Biology, vol 1032. Springer, Cham. https://doi.org/10.1007/978-3-319-98788-0_9

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