Regulation of colon gene expression by vitamin B6 supplementation

Mol Nutr Food Res. 2012 Apr;56(4):641-52. doi: 10.1002/mnfr.201100707.

Abstract

Scope: Previous studies have shown that vitamin B6 supplementation suppresses the development of colonic aberrant crypt foci (ACF), precursor lesions of colon cancer, and cell proliferation in mice receiving the colonic carcinogen, azoxymethane (AOM). This study investigated the molecular mechanism of these effects of dietary vitamin B6.

Methods and results: To date, the mechanism by which ACFs develop is not yet fully understood. In a search for factors that play a critical role during ACF development, we examined colon gene expression during early stage of ACF development in AOM-treated mice using DNA microarray analysis. AOM treatment significantly upregulated mRNA closely related to mast cell and cytotoxic T-cell activity. This study also investigated the effect of vitamin B6 supplementation on colon gene expression in AOM-treated mice. We found that vitamin B6 supplementation downregulates Cd8a and Ccl8 mRNA expression, suggesting these candidate genes may play a protective role against colonic ACF development. Furthermore, we examined genomic affects of dietary vitamin B6, and showed that Reg3γ mRNA expression in colons is downregulated by vitamin B6.

Conclusion: This study provides an insight into the genomic activities of dietary vitamin B6 that may be protective against colon tumor development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aberrant Crypt Foci / genetics*
  • Aberrant Crypt Foci / pathology
  • Aberrant Crypt Foci / prevention & control
  • Animals
  • Azoxymethane / toxicity
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism
  • Cell Proliferation / drug effects
  • Chemokine CCL8 / genetics
  • Chemokine CCL8 / metabolism
  • Colon / drug effects*
  • Colon / metabolism
  • Colon / pathology
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control
  • Dietary Supplements*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Vitamin B 6 / administration & dosage*

Substances

  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Ccl8 protein, mouse
  • Chemokine CCL8
  • RNA, Messenger
  • Vitamin B 6
  • Azoxymethane