Matrine Promotes Human Myeloid Leukemia Cells Apoptosis Through Warburg Effect Mediated by Hexokinase 2
Matrine, an alkaloid compound isolated from the medicinal plant Sophora flavescens, inhibits many types of cancer proliferation. However, the precise mechanism of the matrine antihuman chronic myeloid leukemia remains unclear. In this study, we showed that matrine significantly inhibited the cell pr...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-09-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.01069/full |
| _version_ | 1818517259567497216 |
|---|---|
| author | Guibin Lin Yangzhe Wu Fengtao Cai Zhen Li Shixin Su Jian Wang Jialin Cao Lingdi Ma |
| author_facet | Guibin Lin Yangzhe Wu Fengtao Cai Zhen Li Shixin Su Jian Wang Jialin Cao Lingdi Ma |
| author_sort | Guibin Lin |
| collection | DOAJ |
| description | Matrine, an alkaloid compound isolated from the medicinal plant Sophora flavescens, inhibits many types of cancer proliferation. However, the precise mechanism of the matrine antihuman chronic myeloid leukemia remains unclear. In this study, we showed that matrine significantly inhibited the cell proliferation and induced apoptosis by regulating Warburg effect through controlling hexokinases 2 (HK2) expression in myeloid leukemia cells. Interestingly, matrine inhibited the expression of HK2 mediated by reduction in c-Myc binding to HK2 gene intron and led to downregulation of HK2, which upregulated proapoptotic protein Bad and then induced apoptosis. We further demonstrated that matrine could synergize with lonidamine, an inhibitor of HK2, for the treatment of myeloid leukemia, both in vitro and in vivo. Taken together, our findings reveal that matrine could promote human myeloid leukemia cells apoptosis via regulating Warburg effect by controlling HK2. |
| first_indexed | 2024-12-11T00:53:52Z |
| format | Article |
| id | doaj.art-95e18124705248bba518e73631572a80 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T00:53:52Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-95e18124705248bba518e73631572a802022-12-22T01:26:32ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-09-011010.3389/fphar.2019.01069462055Matrine Promotes Human Myeloid Leukemia Cells Apoptosis Through Warburg Effect Mediated by Hexokinase 2Guibin Lin0Yangzhe Wu1Fengtao Cai2Zhen Li3Shixin Su4Jian Wang5Jialin Cao6Lingdi Ma7Laboratory Center, The Third People’s Hospital of Huizhou, Affiliated Hospital of Guangzhou Medical University, Huizhou, ChinaThe First Affiliated Hospital, Biomedical Translational Research Institute and School of Pharmacy, Jinan University, Guangzhou, ChinaLaboratory Center, The Third People’s Hospital of Huizhou, Affiliated Hospital of Guangzhou Medical University, Huizhou, ChinaThe First Affiliated Hospital, Biomedical Translational Research Institute and School of Pharmacy, Jinan University, Guangzhou, ChinaThe First Affiliated Hospital, Biomedical Translational Research Institute and School of Pharmacy, Jinan University, Guangzhou, ChinaLaboratory Center, The Third People’s Hospital of Huizhou, Affiliated Hospital of Guangzhou Medical University, Huizhou, ChinaLaboratory Center, The Third People’s Hospital of Huizhou, Affiliated Hospital of Guangzhou Medical University, Huizhou, ChinaLaboratory Center, The Third People’s Hospital of Huizhou, Affiliated Hospital of Guangzhou Medical University, Huizhou, ChinaMatrine, an alkaloid compound isolated from the medicinal plant Sophora flavescens, inhibits many types of cancer proliferation. However, the precise mechanism of the matrine antihuman chronic myeloid leukemia remains unclear. In this study, we showed that matrine significantly inhibited the cell proliferation and induced apoptosis by regulating Warburg effect through controlling hexokinases 2 (HK2) expression in myeloid leukemia cells. Interestingly, matrine inhibited the expression of HK2 mediated by reduction in c-Myc binding to HK2 gene intron and led to downregulation of HK2, which upregulated proapoptotic protein Bad and then induced apoptosis. We further demonstrated that matrine could synergize with lonidamine, an inhibitor of HK2, for the treatment of myeloid leukemia, both in vitro and in vivo. Taken together, our findings reveal that matrine could promote human myeloid leukemia cells apoptosis via regulating Warburg effect by controlling HK2.https://www.frontiersin.org/article/10.3389/fphar.2019.01069/fullmatrineleukemiahexokinase 2glycolysisapoptosis |
| spellingShingle | Guibin Lin Yangzhe Wu Fengtao Cai Zhen Li Shixin Su Jian Wang Jialin Cao Lingdi Ma Matrine Promotes Human Myeloid Leukemia Cells Apoptosis Through Warburg Effect Mediated by Hexokinase 2 Frontiers in Pharmacology matrine leukemia hexokinase 2 glycolysis apoptosis |
| title | Matrine Promotes Human Myeloid Leukemia Cells Apoptosis Through Warburg Effect Mediated by Hexokinase 2 |
| title_full | Matrine Promotes Human Myeloid Leukemia Cells Apoptosis Through Warburg Effect Mediated by Hexokinase 2 |
| title_fullStr | Matrine Promotes Human Myeloid Leukemia Cells Apoptosis Through Warburg Effect Mediated by Hexokinase 2 |
| title_full_unstemmed | Matrine Promotes Human Myeloid Leukemia Cells Apoptosis Through Warburg Effect Mediated by Hexokinase 2 |
| title_short | Matrine Promotes Human Myeloid Leukemia Cells Apoptosis Through Warburg Effect Mediated by Hexokinase 2 |
| title_sort | matrine promotes human myeloid leukemia cells apoptosis through warburg effect mediated by hexokinase 2 |
| topic | matrine leukemia hexokinase 2 glycolysis apoptosis |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.01069/full |
| work_keys_str_mv | AT guibinlin matrinepromoteshumanmyeloidleukemiacellsapoptosisthroughwarburgeffectmediatedbyhexokinase2 AT yangzhewu matrinepromoteshumanmyeloidleukemiacellsapoptosisthroughwarburgeffectmediatedbyhexokinase2 AT fengtaocai matrinepromoteshumanmyeloidleukemiacellsapoptosisthroughwarburgeffectmediatedbyhexokinase2 AT zhenli matrinepromoteshumanmyeloidleukemiacellsapoptosisthroughwarburgeffectmediatedbyhexokinase2 AT shixinsu matrinepromoteshumanmyeloidleukemiacellsapoptosisthroughwarburgeffectmediatedbyhexokinase2 AT jianwang matrinepromoteshumanmyeloidleukemiacellsapoptosisthroughwarburgeffectmediatedbyhexokinase2 AT jialincao matrinepromoteshumanmyeloidleukemiacellsapoptosisthroughwarburgeffectmediatedbyhexokinase2 AT lingdima matrinepromoteshumanmyeloidleukemiacellsapoptosisthroughwarburgeffectmediatedbyhexokinase2 |