title: Vitamin B₆ activates p53 and elevates p21 gene expression in cancer cells and the mouse colon.
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.
authors.affiliation: Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
authors.forename: Peipei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
authors.forename: Sofya
authors.initials: S
authors.lastname: Suidasari
authors.affiliation: Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yanaka
authors.affiliation: Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Kato
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000517:prevention & control; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D004032:Diet; D004789:Enzyme Activation / Q000187:drug effects; D057809:HEK293 Cells; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011730:Pyridoxal / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D011730:Pyridoxal