Yiqun Huang1, Yong Zou1, Luhui Lin1, Xudong Ma1, Xiaohong Huang2. 1. Department of Hematology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, China. 2. Department of Pharmacy, Zhangzhou Affiliated Hospital of Fujian Medical University, No. 59 Shengli Road, Zhangzhou, Fujian 363000, China. Electronic address: XiaohongHuang2017@163.com.
Abstract
OBJECTIVE: To 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. METHODS: Cell 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. RESULTS: BIX-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. CONCLUSION: Taken 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.
OBJECTIVE: To 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. METHODS: Cell 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. RESULTS:BIX-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. CONCLUSION: Taken 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.
Authors: John Anthony Yason; Kristine Anne Ru Ping Koh; Kevin Shyong Wei Tan Journal: Antimicrob Agents Chemother Date: 2018-07-27 Impact factor: 5.191
Authors: Elena Madrazo; David Ruano; Lorea Abad; Estefanía Alonso-Gómez; Carmen Sánchez-Valdepeñas; África González-Murillo; Manuel Ramírez; Javier Redondo-Muñoz Journal: Cancers (Basel) Date: 2018-09-12 Impact factor: 6.639