Vitamin B6 suppresses growth and expression of albumin gene in a human hepatoma cell line HepG2.
The effect of vitamin B6 on the growth of a human hepatoma cell line HepG2 in culture was studied. The growth of HepG2 cells and protein synthesis were almost completely inhibited in medium supplemented with 5 mM pyridoxine. Pyridoxal was as effective as pyridoxine, but pyridoxamine showed no inhibitory action. The growth inhibition of HepG2 cells by pyridoxine was accompanied by a marked inhibition of secretion of plasma proteins, particularly albumin. Northern blot analysis of albumin mRNA showed that pyridoxine caused a rapid decrease in the expression of albumin gene. The electron-microscopic examination of pyridoxine-treated HepG2 cells revealed a smoothing of nuclear membrane, a decrease in the number of nucleoli, and an appearance of aggregated heterochromatin structures. These morphological features are compatible with the depressed transcriptional activity in the pyridoxine-treated cells. The mechanism by which vitamin B6 exerts its inhibitory effect was discussed in terms of our recent finding that vitamin B6 modulates expression of albumin gene by inactivating tissue-specific DNA-binding proteins. Binding of pyridoxal phosphate with tissue-specific transcription factors may reduce the capacity of these factors to interact with the regulatory region of albumin gene, resulting in the inhibition of the gene expression.
Molina
A
A
Department of Nutrition, School of Medicine, University of Tokushima, Japan.
Oka
T
T
Muńoz
S M
SM
Chikamori-Aoyama
M
M
Kuwahata
M
M
Natori
Y
Y
D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D011736:Pyridoxine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D012709:Serum Albumin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D011506:Proteins; D012333:RNA, Messenger; D012709:Serum Albumin; D011736:Pyridoxine