Vitamin B6 activates p53 and elevates p21 gene expression in cancer cells and the mouse colon

Zhang,Peipei; Suidasari,Sofya; Hasegawa,Tomomi; Yanaka,Noriyuki; Kato,Norihisa

doi:10.3892/or.2014.3073

Vitamin B6 activates p53 and elevates p21 gene expression in cancer cells and the mouse colon

Authors:
- Peipei Zhang
- Sofya Suidasari
- Tomomi Hasegawa
- Noriyuki Yanaka
- Norihisa Kato
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Affiliations: Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
Published online on: March 11, 2014 https://doi.org/10.3892/or.2014.3073
Pages: 2371-2376

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Abstract

Increasing evidence indicates vitamin B6 acts as a protective factor against colon cancer. However, the mechanisms of the effect of vitamin B6 are poorly understood. The present preliminary study using DNA microarray and real-time PCR indicates p21 mRNA is upregulated in human colon carcinoma (HT29) cells exposed to pyridoxal (PL, 500 µM). A similar effect was observed in human epithelial colorectal adenocarcinoma (Caco2) cells, human colon adenocarcinoma (LoVo) cells, human embryonic kidney (HEK293T) cells, and human hepatoma (HepG2) cells. Adding other B6-vitamers such as pyridoxal 5'-phosphate (PLP), pyridoxine (PN), and pyridoxamine (PM) caused no such effect. In order to understand the mechanism of higher mRNA expression of p21 by PL, effect of PL on the p53 activation was examined (the upstream factor for p21 mRNA transcription) in HT29 cells, LoVo cells, and HepG2 cells. PL increased the phosphorylated p53 protein levels (active form) in whole-cell lysates and the nuclei of the cells. Noteworthy, the consumption of a vitamin B6-deficient diet for 5 weeks significantly reduced p21 mRNA levels and tended to reduce phosphorylated p53 protein levels (P=0.053) in the colons of mice compared to a diet with adequate vitamin B6. Thus, these results suggest vitamin B6 plays a role in increasing p21 gene expression via p53 activation in several cancer cells and the mouse colon.

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