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-neopl...
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doaj-38cc85bc183d4db4957e0375c4eba6ea2020-11-24T23:54:15ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences 2008-38662008-38742016-07-011977797867364Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cellsMarie Saghaeian Jazi0Saeed Mohammadi1Yaghoub Yazdani2Sima Sedighi3Ali Memarian4Mehrdad Aghaei5Student 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, IranStudent 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, IranInfectious Diseases Research Center and Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, IranJoint, Bone, and Connective tissue Research Center (JBCRC), Golestan University of Medical Sciences, Gorgan, IranStem Cell Research Center, Golestan University of Medical Sciences, Gorgan, IranJoint, Bone, and Connective tissue Research Center (JBCRC), Golestan University of Medical Sciences, Gorgan, IranObjective(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.http://ijbms.mums.ac.ir/article_7364_f26a238aaed8f3a1579682510a0d9c35.pdfPioglitazoneProliferationT-cell leukemiaValproic acid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marie Saghaeian Jazi Saeed Mohammadi Yaghoub Yazdani Sima Sedighi Ali Memarian Mehrdad Aghaei |
spellingShingle |
Marie Saghaeian Jazi Saeed Mohammadi Yaghoub Yazdani Sima Sedighi Ali Memarian Mehrdad Aghaei Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells Iranian Journal of Basic Medical Sciences Pioglitazone Proliferation T-cell leukemia Valproic acid |
author_facet |
Marie Saghaeian Jazi Saeed Mohammadi Yaghoub Yazdani Sima Sedighi Ali Memarian Mehrdad Aghaei |
author_sort |
Marie Saghaeian Jazi |
title |
Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells |
title_short |
Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells |
title_full |
Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells |
title_fullStr |
Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells |
title_full_unstemmed |
Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells |
title_sort |
effects of valproic acid and pioglitazone on cell cycle progression and proliferation of t-cell acute lymphoblastic leukemia jurkat cells |
publisher |
Mashhad University of Medical Sciences |
series |
Iranian Journal of Basic Medical Sciences |
issn |
2008-3866 2008-3874 |
publishDate |
2016-07-01 |
description |
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. |
topic |
Pioglitazone Proliferation T-cell leukemia Valproic acid |
url |
http://ijbms.mums.ac.ir/article_7364_f26a238aaed8f3a1579682510a0d9c35.pdf |
work_keys_str_mv |
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