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Front. Pharmacol. | doi: 10.3389/fphar.2019.01069

Matrine promotes human myeloid leukemia cells apoptosis through Warburg effect mediated by hexokinase 2

 Guibin Lin1,  Yangze Wu2, Fengtao Cai1, Zhen Li2, Shixin Su2, Jian Wang1, Jialin Cao1 and Lingdi Ma1*
  • 1The Third People’s Hospital of Huizhou, Affiliated Hospital of Guangzhou Medical University, China
  • 2Biomedical Translational Research Institute, Jinan University, China

Matrine, an alkaloid compound isolated from the medicinal plant Sophora flavescens, inhibits many types cancer proliferation. However, the precise mechanism of the matrine anti-human 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 of c-Myc binding to HK2 gene intron, led to down-regulation of HK2, which up-regulated pro-apoptotic 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.

Keywords: matrine, Leukemia, Hexokinase 2, Glycolysis, Apoptosis

Received: 26 Mar 2019; Accepted: 22 Aug 2019.

Copyright: © 2019 Lin, Wu, Cai, Li, Su, Wang, Cao and Ma. 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.

* Correspondence: Mx. Lingdi Ma, The Third People’s Hospital of Huizhou, Affiliated Hospital of Guangzhou Medical University, Huizhou, China, lingdimawsh@126.com