Liu Hui-Min, Guo Chun-Ling, Zhang Yao-Fang, Chen Jian-Fang, Liang Zhi-Peng, Yang Lin-Hua, Ma Yan-Ping
Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Front Pharmacol. 2021 Apr 16;12:657724. doi: 10.3389/fphar.2021.657724. eCollection 2021.
Leonurine, an active natural alkaloid compound isolated from Herba leonuri, has been reported to exhibit promising anticancer activity in solid tumors. The aim of this study was to explore whether leonurine is able to inhibit chronic myeloid leukemia (CML) malignancy. Here, we found that leonurine dose dependently inhibited the proliferation, migration, colony formation and promoted apoptosis of CML cells. Furthermore, leonurine markedly reduced CML xenograft growth . Mechanically, leonurine upregulated SOCS5 expression, thus leading JAK2/STAT3 signaling suppression. Silencing of SOCS5 by its siRNA abrogated the effect of leonurine on CML cells, demonstrating that SOCS5 mediates the anti-leukemia effect of leonurine. Notably, we observed that miR-18a-5p was remarkably increased in CML cells. Treating CML cells with leonurine significantly decreased miR-18a-5p expression. Moreover, we found miR-18a-5p repressed SOCS5 by directly targeting its 3'-UTR. miR-18a-5p downregulation induced by leonurine reduced the biological activity of CML cells by relieving miR-18a-5p repression of SOCS5 expression. Taken together, leonurine exerts significant anti-leukemia efficacy in CML by regulating miR-18a-5p/SOCS5/JAK2/STAT3 axis.
益母草碱是从益母草中分离得到的一种活性天然生物碱化合物，据报道其在实体瘤中具有良好的抗癌活性。本研究旨在探讨益母草碱是否能够抑制慢性髓性白血病（CML）的恶性进展。在此，我们发现益母草碱剂量依赖性地抑制CML细胞的增殖、迁移、集落形成并促进其凋亡。此外，益母草碱显著降低了CML异种移植瘤的生长。机制上，益母草碱上调了SOCS5的表达，从而导致JAK2/STAT3信号通路受到抑制。通过siRNA沉默SOCS5消除了益母草碱对CML细胞的作用，表明SOCS5介导了益母草碱的抗白血病作用。值得注意的是，我们观察到CML细胞中miR-18a-5p显著升高。用益母草碱处理CML细胞可显著降低miR-18a-5p的表达。此外，我们发现miR-18a-5p通过直接靶向SOCS5的3'-UTR来抑制SOCS5。益母草碱诱导的miR-18a-5p下调通过减轻miR-18a-5p对SOCS5表达的抑制作用，降低了CML细胞的生物学活性。综上所述，益母草碱通过调节miR-18a-5p/SOCS5/JAK2/STAT3轴在CML中发挥显著的抗白血病疗效。
