A. Molina et al., VITAMIN-B-6 SUPPRESSES GROWTH AND EXPRESSION OF ALBUMIN GENE IN A HUMAN HEPATOMA-CELL LINE HEPG2, Nutrition and cancer, 28(2), 1997, pp. 206-211
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.