title: 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.
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.
authors: Department of Veterinary Pathobiology, Faculty of Agriculture, Kagoshima University, Kagoshima, Japan.
authors: Miwa
authors: M
authors: Nakari
authors: Hiroaki
authors: H
authors: Kanouchi
authors: Tatsuzo
authors: T
authors: Oka
mesh_terms: D000097:Acetonitriles / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D020411:Oligonucleotide Array Sequence Analysis; D011736:Pyridoxine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C489138:1,3-benzothiazol-2-yl(2-((2-(3-pyridinyl)ethyl)amino)-4-pyrimidinyl)acetonitrile; D000097:Acetonitriles; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D007093:Imidazoles; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D014803:Vitamin B Complex; D014050:Toluene; C121565:pifithrin; D020928:Mitogen-Activated Protein Kinases; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole; D011736:Pyridoxine