title: Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran; Department of Molecular Medicine, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Marie Saghaeian
authors.initials: MS
authors.lastname: Jazi
authors.affiliation: Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran; Department of Molecular Medicine, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Mohammadi
authors.affiliation: Infectious Diseases Research Center and Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Yazdani
authors.affiliation: Joint, Bone, and Connective tissue Research Center (JBCRC), Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Sima
authors.initials: S
authors.lastname: Sedighi
authors.affiliation: Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Memarian
authors.affiliation: Joint, Bone, and Connective tissue Research Center (JBCRC), Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Aghaei
keywords: Pioglitazone; Proliferation; T-cell leukemia; Valproic acid