Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells

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SAGHAEIAN JAZI MARIE; MOHAMMADI SAEED; YAZDANI YAGHOUB; SEDIGHI SIMA; MEMARIAN ALI; AGHAEI MEHRDAD

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Journal: Iranian Journal of Basic Medical Sciences Year:2016 | Volume:19 | Issue:7 Page(s): 779-786

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Title

Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells

Author(s)

Keywords

Pioglitazone

Proliferation

T-cell leukemia

Valproic acid

Abstract

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 μ M 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.

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APA: Copy

SAGHAEIAN JAZI, MARIE, MOHAMMADI, SAEED, YAZDANI, YAGHOUB, SEDIGHI, SIMA, MEMARIAN, ALI, & AGHAEI, MEHRDAD. (2016). 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, 19(7), 779-786. SID. https://sid.ir/paper/721626/en

Vancouver: Copy

SAGHAEIAN JAZI MARIE, MOHAMMADI SAEED, YAZDANI YAGHOUB, SEDIGHI SIMA, MEMARIAN ALI, AGHAEI MEHRDAD. 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[Internet]. 2016;19(7):779-786. Available from: https://sid.ir/paper/721626/en

IEEE: Copy

MARIE SAGHAEIAN JAZI, SAEED MOHAMMADI, YAGHOUB YAZDANI, SIMA SEDIGHI, ALI MEMARIAN, and 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, vol. 19, no. 7, pp. 779–786, 2016, [Online]. Available: https://sid.ir/paper/721626/en

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