Abstract
It has been reported that supplementation with high-dose vitamin B(6) (B(6)) exerts antitumor effects in rodent models of cancer. However, the mechanism of these effects remains poorly understood. High-dose B(6) 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.
MeSH terms
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Acetonitriles / pharmacology
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects
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Benzothiazoles / pharmacology
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Breast Neoplasms / drug therapy
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Breast Neoplasms / metabolism*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dietary Supplements
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Dose-Response Relationship, Drug
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Female
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Gene Expression / drug effects*
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Humans
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Imidazoles / pharmacology
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Insulin-Like Growth Factor Binding Protein 3 / genetics
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Insulin-Like Growth Factor Binding Protein 3 / metabolism*
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Oligonucleotide Array Sequence Analysis
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Pyridoxine / administration & dosage
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Pyridoxine / pharmacology*
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Pyridoxine / therapeutic use
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RNA, Messenger / biosynthesis
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Real-Time Polymerase Chain Reaction
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Toluene / analogs & derivatives
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Toluene / pharmacology
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Tumor Suppressor Protein p53 / antagonists & inhibitors
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Tumor Suppressor Protein p53 / metabolism*
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Vitamin B Complex / administration & dosage
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Vitamin B Complex / pharmacology*
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Vitamin B Complex / therapeutic use
Substances
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1,3-benzothiazol-2-yl(2-((2-(3-pyridinyl)ethyl)amino)-4-pyrimidinyl)acetonitrile
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Acetonitriles
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Antineoplastic Agents
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Benzothiazoles
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Imidazoles
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Insulin-Like Growth Factor Binding Protein 3
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RNA, Messenger
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Tumor Suppressor Protein p53
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Vitamin B Complex
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Toluene
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pifithrin
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Mitogen-Activated Protein Kinases
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2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole
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Pyridoxine