Bromodomains and Extra-Terminal (BET) Inhibitor JQ1 Suppresses Proliferation of Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolysis
| Autor: | Zhong-Hua Tang, Wei-Wei Zheng, Cai-Wen Duan, Sheng-Li Liu, Hang Zhou, Wen-Li Huang, Tuersunayi Abudureheman, Neng Zhou, Da-Bin Tang, Meng-Yi Zhang, Bin-Bing S. Zhou |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cell Survival
Genes myc Apoptosis Cell Cycle Proteins 030204 cardiovascular system & hematology Proto-Oncogene Proteins c-myc BET inhibitor 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lab/In Vitro Research Cell Line Tumor Lactate dehydrogenase Humans Glycolysis Cell Proliferation Chemistry Cell growth Cell Cycle Nuclear Proteins Proteins Azepines Cell Cycle Checkpoints General Medicine Precursor Cell Lymphoblastic Leukemia-Lymphoma Triazoles Cell cycle HEK293 Cells Cell culture 030220 oncology & carcinogenesis Cancer research Transcription Factors Phosphofructokinase |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 |
| Popis: | BACKGROUND Acute lymphocytic leukemia (ALL) is a common blood cancer which induces high mortality in children. Bromodomains and extra-terminal (BET) protein inhibitors, such as JQ1 and ARV-825, are promising cancer therapeutic agents that can be used by targeting c-Myc. A recent work reported that JQ1 effectively attenuates ALL in vitro by suppressing cell proliferation and accelerating apoptosis. The purpose of this research was to probe into the potential mechanism of how JQ1 inhibits ALL cell proliferation in vitro. MATERIAL AND METHODS Cell viability of ALL cells were measured by CTG after treatment by JQ1. Cell cycle analysis was done by EdU and PI staining. Cell apoptosis was assessed by Annexin V/PI staining. Glycolysis was detected using Seahorse and LC-MS kits. The expression of glycolytic rate-limiting enzymes was assessed by RNA-seq, qRT-PCR, and Western blot. RESULTS JQ1 suppressed cell proliferation by arresting the cell cycle and inducing the apoptosis of acute lymphocytic leukemia cells. JQ1 inhibited cell proliferation of B-ALL cells by restraining glycolysis. Conversely, the cell cycle block of B-ALL cells induced by JQ1 was partially abolished after pretreatment with 2-Deoxy-D-glucose (2-DG), an inhibitor of glycolysis. Furthermore, JQ1 restrained the glycolysis of B-ALL cell lines by remarkably downregulating the rate-limiting enzymes of glycolysis, such as hexokinase 2, phosphofructokinase, and lactate dehydrogenase A. Moreover, the cell cycle arrest was reversed in B-ALL cells with overexpressed c-Myc treated by JQ1, which is involved in the enhancement of glycolysis. CONCLUSIONS The BET inhibitor JQ1 suppresses the proliferation of ALL by inhibiting c-Myc-mediated glycolysis, thus providing a new strategy for the treatment of ALL. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|