Lin Guibin, Wu Yangzhe, Cai Fengtao, Li Zhen, Su Shixin, Wang Jian, Cao Jialin, Ma Lingdi
Laboratory Center, The Third People's Hospital of Huizhou, Affiliated Hospital of Guangzhou Medical University, Huizhou, China.
The First Affiliated Hospital, Biomedical Translational Research Institute and School of Pharmacy, Jinan University, Guangzhou, China.
Front Pharmacol. 2019 Sep 24;10:1069. doi: 10.3389/fphar.2019.01069. eCollection 2019.
Matrine, an alkaloid compound isolated from the medicinal plant , 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 and . Taken together, our findings reveal that matrine could promote human myeloid leukemia cells apoptosis regulating Warburg effect by controlling HK2.
苦参碱是从药用植物中分离出的一种生物碱化合物，可抑制多种癌症的增殖。然而，苦参碱抗人类慢性髓性白血病的确切机制仍不清楚。在本研究中，我们发现苦参碱通过控制髓系白血病细胞中己糖激酶2（HK2）的表达来调节瓦伯格效应，从而显著抑制细胞增殖并诱导细胞凋亡。有趣的是，苦参碱通过减少c-Myc与HK2基因内含子的结合来抑制HK2的表达，导致HK2下调，进而上调促凋亡蛋白Bad并诱导细胞凋亡。我们进一步证明，苦参碱可与HK2抑制剂氯尼达明协同治疗髓系白血病。综上所述，我们的研究结果表明，苦参碱可通过控制HK2调节瓦伯格效应，从而促进人类髓系白血病细胞凋亡。
