Parallel treatment with valproic acid and all-trans retinoic acid does not potentiate P21 expression in U-937 PML/RAR cells
Abstract
We studied effect of valproic acid, a representative of histondeacetylases inhibitors, on cell cycle and protein expression in U-937 PML/RAR cells of human histiocytic lymphoma. Moreover, we tried to potentiate its effect by concomitant treatment with the differentiation agent all-trans retinoic acid.
We proved acetylation of nuclear histones H3 and H4 after VA treatment. Activation of non-histone proteins (as p21) preceded this acetylation.
Protein p21 as an inhibitor of cyclin dependent kinases causes cell cycle arrest in G1, resulting in a decrease of the percentage of cells in the S phase, as well as in the inhibition of the proliferation, which we demonstrated after VA treatment. Using concomitant treatment with VA and ATRA failed to yield a synergistic or additive effect on p21 expression in our experiments.
Thus different treatment schedules should be the aim of further studies.