Role of polyamines in arginine-dependent colon carcinogenesis in Apc Min/+ mice

Hagit F. Yerushalmi, David G. Besselsen, Natalia A. Ignatenko, Karen A. Blohm-Mangone, Jose L. Padilla-Torres, David E. Stringer, Jose M. Guillen, Hana Holubec, Claire M. Payne, Eugene W. Gerner

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

We evaluated the role of polyamines in arginine-dependent intestinal tumorigenesis in ApcMin/+ mice. Arginine is a substrate for ornithine synthesis and thus can influence polyamine production. Supplementing the diet with arginine increased intestinal and colonic polyamine levels and colonic carcinogenesis. Inhibiting polyamine synthesis with D,L-α- diflouromethylornithine (DFMO) decreased small intestinal and colonic polyamine pools. In mice provided basal diet, but not when supplemented with arginine, DFMO decreased small intestinal tumor number and burden, and increased intestinal apoptosis. In mice provided supplemental arginine in the diet, DFMO induced late apoptosis and decreased tumorigenesis in the colon. DFMO slightly reduced tumor incidence, number, and size while significantly decreasing tumor burden and grade. These changes in colon tumorigenesis did not occur in mice not provided supplemental arginine. Our study indicates that polyamines play unique roles in intestinal and colonic carcinogenesis in ApcMin/+ mice. Inhibition of polyamine synthesis suppresses the arginine-dependent risk of colon tumorigenesis, resulting in apoptosis induction and decreased tumorigenesis, in this murine model.

Original languageEnglish (US)
Pages (from-to)764-773
Number of pages10
JournalMolecular Carcinogenesis
Volume45
Issue number10
DOIs
StatePublished - Oct 1 2006

Keywords

  • Arginine
  • D,L-α-diflouromethylornithine (DFMO)
  • Intestinal and colonic carcinogenesis
  • Min mice
  • Polyamines

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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  • Cite this

    Yerushalmi, H. F., Besselsen, D. G., Ignatenko, N. A., Blohm-Mangone, K. A., Padilla-Torres, J. L., Stringer, D. E., Guillen, J. M., Holubec, H., Payne, C. M., & Gerner, E. W. (2006). Role of polyamines in arginine-dependent colon carcinogenesis in Apc Min/+ mice. Molecular Carcinogenesis, 45(10), 764-773. https://doi.org/10.1002/mc.20246