effects of valproic acid and pioglitazone on cell cycle progression and proliferation of t-cell acute lymphoblastic leukemia jurkat cells

objective(s): t-cell acute lymphoblastic leukemia (t-all) is an aggressive hematologic malignant tumor. administration of chemical compounds influencing apoptosis and t cell development has been discussed as promising novel therapeutic strategies. valproic acid (vpa) as a recently emerged anti-neoplastic histone deacetylase (hdac) inhibitor and pioglitazone (pgz) as a high-affinity peroxisome proliferator-activated receptor-gamma (pparγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies. here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human jurkat cells. materials and methods: treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and mtt viability assay. real-time rt-pcr was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. results: our findings illustrated that both vpa and pgz can inhibit jurkat e6.1 cells in vitro after   24 hr; however, pgz 400 μm presents the most anti-proliferative effect. interestingly, treated cells have been arrested in g2/m with deregulated cell division cycle 25a (cdc25a) phosphatase and cyclin-dependent kinase inhibitor 1b (cdkn1b or p27) expression. expression of cyclin d1 gene was inhibited when dna synthesis entry was declined. cell cycle deregulation in pgz and vpa-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. conclusion: these findings define that anti-proliferative effects of pgz and vpa on jurkat cell line are mediated by cell cycle deregulation. thus, we suggest pgz and vpa may relieve potential therapeutic application against apoptosis-resistant malignancies.