title: Vitamin B6 suppresses serine protease inhibitor 3 expression in the colon of rats and in TNF-α-stimulated HT-29 cells.
abstract: METHODS
  Previous reports in the areas of animal studies and, recently epidemiology, have linked anti-tumorigenic and anti-inflammatory effects to dietary vitamin B6. This study investigated the molecular mechanism of these effects of vitamin B6.
  
  
  RESULTS
  DNA microarray analysis was used to obtain information on changes in colon gene expression from vitamin B6 (pyridoxine) repletion in vitamin B6-deficient rats. Pyridoxine supplementation down-regulated the inflammatory molecule, serine protease inhibitor clade A member 3 (SPI-3) mRNA expression in the colon. This study also showed that tumor necrosis factor α (TNF-α) induced SPI-3 mRNA expression in HT-29 human colon cancer cells, and vitamin B6 (pyridoxal hydrochloride) pretreatment of HT-29 cells inhibited TNF -induced mRNA expression of SPI-3. Vitamin B6 inhibited TNF-α-induced NF-κB activation via suppression of IκBα degradation in HT-29 cells. HT-29 cells stably expressing epitope-tagged ubiquitin were generated and vitamin B6 pretreatment was shown to inhibit ubiquitination of the IkB protein in response to TNF-α-i.
  
  
  CONCLUSIONS
  Vitamin B6 suppressed SPI-3 expression in the colon of rats and in TNF-α-stimulated HT-29 cells. Further, this study showed a possible role of vitamin B6 in the regulation of protein ubiquitination.
authors.affiliation: Department of Bioresource Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Japan. yanaka@hiroshima-u.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yanaka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ohata
authors.forename: Keigo
authors.initials: K
authors.lastname: Toya
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kanda
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hirata
authors.forename: Norihisa
authors.initials: N
authors.lastname: Kato
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D005786:Gene Expression Regulation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D054875:Ubiquitination; D025101:Vitamin B 6 / Q000378:metabolism* / Q000627:therapeutic use; D026681:Vitamin B 6 Deficiency / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000209:Acute-Phase Proteins; D016588:Anticarcinogenic Agents; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D011994:Recombinant Proteins; C516148:SERPINA3 protein, human; C403317:Serpina3n protein, rat; D015843:Serpins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D025101:Vitamin B 6