Matrine Promotes Human Myeloid Leukemia Cells Apoptosis Through Warburg Effect Mediated by Hexokinase 2
Matrine Promotes Human Myeloid Leukemia Cells Apoptosis Through Warburg Effect Mediated by Hexokinase 2
复制标题
苦参碱通过己糖激酶2介导的Warburg效应促进人髓系白血病细胞凋亡
DOI：
10.3389/fphar.2019.01069
复制
发表时间：
2019-09-24
影响因子：
5.6
通讯作者：
Ma, Lingdi
中科院分区：
文献类型：
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作者：
Lin, Guibin;Wu, Yangzhe;Ma, Lingdi
苦参碱是从药用植物苦参中分离出来的一种生物碱化合物，可以抑制多种类型的癌症增殖。然而，苦参碱抗人慢性粒细胞白血病的确切作用机制尚不清楚。在本研究中，我们发现苦参碱通过调控髓系白血病细胞中己糖激酶2(HK2)的表达来调节Warburg效应，从而显著抑制细胞增殖和诱导细胞凋亡。有趣的是，苦参碱通过减少c-Myc与HK2基因内含子的结合而抑制HK2的表达，并导致HK2表达下调，从而上调促凋亡蛋白Bad，从而诱导细胞凋亡。我们进一步证明，苦参碱在体外和体内都能与HK2的抑制剂氯硝胺协同治疗髓系白血病。综上所述，我们的研究结果表明，苦参碱可能通过调控HK2来调节Warburg效应，从而促进人髓系白血病细胞的凋亡。
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.