کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5527696 1547885 2017 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research paperEffect of BIX-01294 on proliferation, apoptosis and histone methylation of acute T lymphoblastic leukemia cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Research paperEffect of BIX-01294 on proliferation, apoptosis and histone methylation of acute T lymphoblastic leukemia cells
چکیده انگلیسی


- BIX-01294 inhibits Bcl-2, upregulates Bax and caspase-3 and induces cell apoptosis.
- BIX-01294 upregulates P21 and induces cell cycle arrest in the phase G0/G1.
- BIX-01294 downregulates histone H3K9 mono- and di-methylation levels.
- BIX-01294 inhibits the proliferation of acute T lymphoblastic leukemia cells.

ObjectiveTo determine effect of G9a inhibitor BIX-01294 on proliferation, apoptosis and histone methylation of acute T lymphoblastic leukemia cells (MOLT-4 and Jurkat) and to explore the underlying mechanism.MethodsCell proliferation was detected by MTT assay and apoptosis and cell cycle were measured by flow cytometry. Western blot was performed to determine expression of caspase-3, Bcl-2, Bax, P21, P15 and DNMT1 as well as levels of histone H3 acetylation, histone H3K9 mono- di- and tri-methylation.ResultsBIX-01294 inhibits expression of Bcl-2, upregulates expression of Bax and caspase-3 and induces cell apoptosis. BIX-01294 upregulates cell cycle inhibitor P21 expression and induces cell cycle arrest in the phase G0/G1. Furthermore, BIX-01294 suppresses expression of DNA demethylase DNMT1 and promotes expression of tumor suppressor protein P15, thereby inhibiting proliferation of MOLT-4 and Jurkat cells. BIX-01294 downregulates histone H3K9 mono- and di-methylation levels and has no effect on H3K9 trimethylation and histone H3 acetylation.ConclusionTaken together, our results indicate that by regulating H3K9 methylation and cell cycle, BIX-01294 inhibits the proliferation and induces apoptosis of acute T lymphoblastic leukemia cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 62, November 2017, Pages 34-39
نویسندگان
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