Effect of BIX-01294 on proliferation, apoptosis and histone methylation 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.