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CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism
B-cell acute lymphocytic leukemia (B-ALL), a common blood cancer in children, leads to high mortality. Cyclin-dependent kinase 9 inhibitor (CDK9i) effectively attenuates acute myeloid leukemia and chronic lymphoblastic leukemia by inducing apoptosis and inhibiting cell proliferation. However, the ef...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969802/ https://www.ncbi.nlm.nih.gov/pubmed/33748130 http://dx.doi.org/10.3389/fcell.2021.641271 |
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author | Huang, Wen-Li Abudureheman, Tuersunayi Xia, Jing Chu, Lei Zhou, Hang Zheng, Wei-Wei Zhou, Neng Shi, Rong-Yi Li, Ming-Hao Zhu, Jian-Min Qing, Kai Ji, Chao Liang, Kai-Wei Guo, Sa Yin, Gang Duan, Cai-Wen |
author_facet | Huang, Wen-Li Abudureheman, Tuersunayi Xia, Jing Chu, Lei Zhou, Hang Zheng, Wei-Wei Zhou, Neng Shi, Rong-Yi Li, Ming-Hao Zhu, Jian-Min Qing, Kai Ji, Chao Liang, Kai-Wei Guo, Sa Yin, Gang Duan, Cai-Wen |
author_sort | Huang, Wen-Li |
collection | PubMed |
description | B-cell acute lymphocytic leukemia (B-ALL), a common blood cancer in children, leads to high mortality. Cyclin-dependent kinase 9 inhibitor (CDK9i) effectively attenuates acute myeloid leukemia and chronic lymphoblastic leukemia by inducing apoptosis and inhibiting cell proliferation. However, the effect of CDK9i on B-ALL cells and the underlying mechanisms remain unclear. In this study, we showed that CDK9i induced the apoptosis of B-ALL cells in vitro by activating the apoptotic pathways. In addition, CDK9i restrained the glycolytic metabolism of B-ALL cells, and CDK9i-induced apoptosis was enhanced by co-treatment with glycolysis inhibitors. Furthermore, CDK9i restained the glycolysis of B-ALL cell lines by markedly downregulating the expression of glucose transporter type 1 (GLUT1) and the key rate-limiting enzymes of glycolysis, such as hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Moreover, cell apoptosis was rescued in B-ALL cells with over-expressed c-Myc after treatment with CDK9i, which is involved in the enhancement of glycolytic metabolism. In summary, our findings suggest that CDK9 inhibitors induce the apoptosis of B-ALL cells by inhibiting c-Myc-mediated glycolytic metabolism, thus providing a new strategy for the treatment of B-ALL. |
format | Online Article Text |
id | pubmed-7969802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79698022021-03-19 CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism Huang, Wen-Li Abudureheman, Tuersunayi Xia, Jing Chu, Lei Zhou, Hang Zheng, Wei-Wei Zhou, Neng Shi, Rong-Yi Li, Ming-Hao Zhu, Jian-Min Qing, Kai Ji, Chao Liang, Kai-Wei Guo, Sa Yin, Gang Duan, Cai-Wen Front Cell Dev Biol Cell and Developmental Biology B-cell acute lymphocytic leukemia (B-ALL), a common blood cancer in children, leads to high mortality. Cyclin-dependent kinase 9 inhibitor (CDK9i) effectively attenuates acute myeloid leukemia and chronic lymphoblastic leukemia by inducing apoptosis and inhibiting cell proliferation. However, the effect of CDK9i on B-ALL cells and the underlying mechanisms remain unclear. In this study, we showed that CDK9i induced the apoptosis of B-ALL cells in vitro by activating the apoptotic pathways. In addition, CDK9i restrained the glycolytic metabolism of B-ALL cells, and CDK9i-induced apoptosis was enhanced by co-treatment with glycolysis inhibitors. Furthermore, CDK9i restained the glycolysis of B-ALL cell lines by markedly downregulating the expression of glucose transporter type 1 (GLUT1) and the key rate-limiting enzymes of glycolysis, such as hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Moreover, cell apoptosis was rescued in B-ALL cells with over-expressed c-Myc after treatment with CDK9i, which is involved in the enhancement of glycolytic metabolism. In summary, our findings suggest that CDK9 inhibitors induce the apoptosis of B-ALL cells by inhibiting c-Myc-mediated glycolytic metabolism, thus providing a new strategy for the treatment of B-ALL. Frontiers Media S.A. 2021-03-04 /pmc/articles/PMC7969802/ /pubmed/33748130 http://dx.doi.org/10.3389/fcell.2021.641271 Text en Copyright © 2021 Huang, Abudureheman, Xia, Chu, Zhou, Zheng, Zhou, Shi, Li, Zhu, Qing, Ji, Liang, Guo, Yin and Duan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Huang, Wen-Li Abudureheman, Tuersunayi Xia, Jing Chu, Lei Zhou, Hang Zheng, Wei-Wei Zhou, Neng Shi, Rong-Yi Li, Ming-Hao Zhu, Jian-Min Qing, Kai Ji, Chao Liang, Kai-Wei Guo, Sa Yin, Gang Duan, Cai-Wen CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism |
title | CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism |
title_full | CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism |
title_fullStr | CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism |
title_full_unstemmed | CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism |
title_short | CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism |
title_sort | cdk9 inhibitor induces the apoptosis of b-cell acute lymphocytic leukemia by inhibiting c-myc-mediated glycolytic metabolism |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969802/ https://www.ncbi.nlm.nih.gov/pubmed/33748130 http://dx.doi.org/10.3389/fcell.2021.641271 |
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