High Dose of Pyridoxine Induces IGFBP-3 mRNA Expression in MCF-7 Cells and Its Induction Is Inhibited by the p53-Specific Inhibitor Pifithrin-α
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概要
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It has been reported that supplementation with high-dose vitamin B6 (B6) exerts antitumor effects in rodent models of cancer. However, the mechanism of these effects remains poorly understood. High-dose B6 also suppresses cell proliferation and induces apoptosis of human breast adenocarcinoma MCF-7 cells. Based on preliminary experiments using DNA microarray analyses, we hypothesized that high-dose pyridoxine (PN) might induce IGF-binding protein-3 (IGFBP-3) expression in MCF-7 cells. In this study, we investigated IGFBP-3 induction by 3 or 10 mM PN using a quantitative real-time PCR method. We found that the induction reached a maximum of 24-fold with 10 mM PN for 72 h compared with non-treated cells. The induction of IGFBP-3 by PN was inhibited by a p53-specific inhibitor, pifithrin-α, in a dose-dependent manner, but was not affected by PD169316 (MAPK inhibitor), AS601245 (c-Jun N-terminal kinase inhibitor) or SL327 (MEK1/2 inhibitor). High-dose PN did not induce p53 mRNA expression. The IGFBP-3 induction by PN seemed to be related to p53 activation.
著者
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Oka Tatsuzo
Department Of Nutrition School Of Medicine The University Of Tokushima
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Kanouchi Hiroaki
Department Of Biochemistry Kawasaki Medical School
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NAKARI Miwa
Department of Veterinary Pathobiology, Faculty of Agriculture, Kagoshima University
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