Vitamin B6 suppresses growth and expression of albumin gene in a human hepatoma cell line HepG2

Abstract

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.

Synthesis, structure and cytotoxicity of diorganotin(IV) complexes of 2,6-lutidine-α2,3-diol (Lu): The crystal structures of Lu and [SnMe2(H2O)(Lu-2H)]

“…The Lu and PN ligands (despite PN is active against the hepatoma cell line HepG2 [26], the human pancreatic carcinoma cell line PANC-1 [27] and the feline mammary tumour cell line FRM [28]) showed a low activity and, as in other cases [29], the activities of the complexes decreased as the size of the R substituent decreased; the Me and Et derivatives had a low activity that made determination of the IC 50 value unwarranted.…”

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

“…Analyses of PN supplementation in cancer animal models (azoxymethane-induced colon tumorigenesis and 7,12-dimethylbenzanthracene-induced mammary tumorigenesis) revealed that high-dose PN prevented tumor progression ( 14 , 15 ). In human hepatoma HepG2 cells ( 16 ) or feline mammary tumor FRM cells ( 17 ), highdose B 6 was found to inhibit cell growth and induce apoptosis. However, the mechanism of the antitumor effects of B 6 has not yet been elucidated.…”

Vitamin B6Suppresses Growth of the Feline Mammary Tumor Cell Line FRM

“…3) On the other hand, Molina and co-workers showed that growth of HepG2 cells, a human hepatoma cell line, was severely inhibited by the addition of high levels of pyridoxine (PN) to a culture medium, and growth inhibition was accompanied by a marked inhibition of expression of the albumin gene. 4) More recent studies have shown that dietary supplementation with vitamin B 6 markedly suppressed azoxymethane-induced colon carcinogenesis in mice by reducing cell proliferation. 5) Thus supraphysiological doses of vitamin B 6 appear to reduce tumor cell growth.…”