Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells
- سال انتشار: 1395
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 19، شماره: 7
- کد COI اختصاصی: JR_IJBMS-19-7_012
- زبان مقاله: انگلیسی
- تعداد مشاهده: 252
نویسندگان
Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
Infectious Diseases Research Center and Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, Iran
Joint, Bone, and Connective tissue Research Center (JBCRC), Golestan University of Medical Sciences, Gorgan, Iran
Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran
Joint, Bone, and Connective tissue Research Center (JBCRC), Golestan University of Medical Sciences, Gorgan, Iran
چکیده
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 E۶.۱ cells in vitro after ۲۴ hr; however, PGZ ۴۰۰ μM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G۲/M with deregulated cell division cycle ۲۵A (Cdc۲۵A) phosphatase and cyclin-dependent kinase inhibitor ۱B (CDKN۱B or p۲۷) expression. Expression of cyclin D۱ 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.کلیدواژه ها
Pioglitazone, Proliferation, T-cell leukemia, Valproic acidاطلاعات بیشتر در مورد COI
COI مخفف عبارت CIVILICA Object Identifier به معنی شناسه سیویلیکا برای اسناد است. COI کدی است که مطابق محل انتشار، به مقالات کنفرانسها و ژورنالهای داخل کشور به هنگام نمایه سازی بر روی پایگاه استنادی سیویلیکا اختصاص می یابد.
کد COI به مفهوم کد ملی اسناد نمایه شده در سیویلیکا است و کدی یکتا و ثابت است و به همین دلیل همواره قابلیت استناد و پیگیری دارد.