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.
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 p...متن کامل
Mir-55 inhibition can reduce cell proliferation and induce apoptosis in Jurkat (Acute T cell Leukemia) cell line
Background MicroRNAs are small and non-coding RNA molecules with approximately 22 nt in length that cause inhibition of translation or degradation of mRNA. MiR-155 is a kind of molecule with different functions, such as its role in proliferation, apoptosis, inflammation, differentiation, and immunity. One of its best known functions is apoptosis that affects on caspase-3 activity. The main aim...متن کامل
Anti-proliferative Effects of Prunus Armeniaca Semen on Acute Leukemia by Regulate of Cell Cycle Progression
Introduction: Prunus armeniaca is one member of the Rosaceae family. Antitumor activity of this family on the colon, prostate, bladder, cervix, lung and breast cancers has been proven in previous research, which is attributed to a natural compound called amygdalin. Therefore, in this study, we investigated the effect of apricot kernel extract on acute leukemia that has not been studied before. ...متن کامل
The Effect of Gaillardin on Proliferation and Apoptosis of Acute Lymphoblastic Leukemia Cell Line (Nalm-6)
Background: Due to increased cancer chemotherapy resistance, the use of natural compounds in cancer treatment has been considered in recent years. Inula-Oculus-Christi, is one of the high importance plants in the field of traditional medicine. It has been shown that extract of this plant has cytotoxic effects on breast cancer cells. Objective: Therefore, the aim of this study was to evaluate t...متن کامل
Background & Objective: Acute lymphoblastic leukemia (ALL) is a malignant disease that arises from various mutations in B or T-lymphoid progenitors. MicroRNAs (miRNAs) regulate gene expression by binding to the 3' untranslated region of protein-coding genes. Dysregulation of miRNA expression m...متن کامل
دوره 19 شماره 7
صفحات 779- 786
تاریخ انتشار 2016-07-01
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