VITAMIN-B-6 SUPPRESSES GROWTH AND EXPRESSION OF ALBUMIN GENE IN A HUMAN HEPATOMA-CELL LINE HEPG2

The effect of vitamin B-6 on the growth of a human hepatoma cell line HepG2 in culture was studied. The growth of HepG2 cells and protein sy nthesis were almost completely inhibited in medium supplemented with 5 mM pyridoxine. Pyridoxal was as effective as pyridoxine, but pyridoxa mine 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 album in mRNA showed that pyridoxine caused a rapid decrease in the expressi on of albumin gene. The electron-microscopic examination of pyridoxine -treated HepG2 cells revealed a smoothing of nuclear membrane, a decre ase in the number of nucleoli, and an appearance of aggregated heteroc hromatin structures. These morphological features are compatible with the depressed transcriptional activity in the pyridoxine-treated cells . The mechanism by which vitamin BThe effect of vitamin B-6 on the gro wth of a human hepatoma cell line HepG2 in culture was studied. The gr owth of HepG2 cells and protein synthesis were almost completely inhib ited in medium supplemented with 5 mM pyridoxine. Pyridoxal was as eff ective as pyridoxine, but pyridoxamine showed no inhibitory action. Th e growth inhibition of HepG2 cells by pyridoxine was accompanied by a marked inhibition of secretion of plasma proteins, particularly albumi n. Northern blot analysis of albumin mRNA showed that pyridoxine cause d a rapid decrease in the expression of albumin gene. The electron-mic roscopic examination of pyridoxine-treated HepG2 cells revealed a smoo thing of nuclear membrane, a decrease in the number of nucleoli, and a n appearance of aggregated heterochromatin structures. These morpholog ical features are compatible with the depressed transcriptional activi ty in the pyridoxine-treated cells. The mechanism by which vitamin B-6 exerts its inhibitory effect was discussed in tel-ms of our recent fi nding that vitamin B-6 modulates expression of albumin gene by inactiv ating tissue-specific DNA-binding proteins. Binding of pyridoxal phosp hate with tissue-specific transcription factors may reduce the capacit y of these factors to interact with the regulatory region of albumin g ene, resulting in the inhibition of the gene expression. exerts its in hibitory effect was discussed in tel-ms of our recent finding that vit amin Bn modulates expression of albumin gene by inactivating tissue-sp ecific DNA-binding proteins. Binding of pyridoxal phosphate with tissu e-specific transcription factors may reduce the capacity of these fact ors to interact with the regulatory region of albumin gene, resulting in the inhibition of the gene expression.