2. Academic Validation
  3. Matrine induces autophagic cell death by triggering ROS/AMPK/mTOR axis and apoptosis in multiple myeloma

Matrine induces autophagic cell death by triggering ROS/AMPK/mTOR axis and apoptosis in multiple myeloma

  • Biomed Pharmacother. 2024 Jun:175:116738. doi: 10.1016/j.biopha.2024.116738.
Xue Li 1,  Jifan Zhou 2,  Yixin Ling 1,  Yicheng Tan 3,  Jialing Zhang 4,  Xiaofang Wang 1,  Fanfan Li 1,  Songfu Jiang 1,  Shenghui Zhang 5,  Kang Yu 6,  Yixiang Han 7
Affiliations

Affiliations

  • 1 Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Institute of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China; Wenzhou Key Laboratory of Hematology, Wenzhou, Zhejiang, China.
  • 2 Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Institute of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 3 Institute of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China; Wenzhou Key Laboratory of Hematology, Wenzhou, Zhejiang, China; Laboratory Animal Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 4 Institute of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China; Wenzhou Key Laboratory of Hematology, Wenzhou, Zhejiang, China; Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 5 Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Institute of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China; Wenzhou Key Laboratory of Hematology, Wenzhou, Zhejiang, China; Laboratory Animal Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: zhangshenghui@wmu.edu.cn.
  • 6 Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Institute of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China; Wenzhou Key Laboratory of Hematology, Wenzhou, Zhejiang, China. Electronic address: yukang62@126.com.
  • 7 Institute of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China; Wenzhou Key Laboratory of Hematology, Wenzhou, Zhejiang, China; Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: yxhan2001@163.com.
PMID: 38759291 DOI: 10.1016/j.biopha.2024.116738
Abstract

Despite significant advancements in multiple myeloma (MM) treatment in recent years, most patients will eventually develop resistance or experience relapse. Matrine, a primary active compound of traditional Chinese medicinal herb Sophora flavescens Ait, has been found to have anti-tumor properties in various types of malignant tumors. Whether Autophagy plays a crucial role in the anti-MM effect of matrine remain unknown. Herein, we found that matrine could trigger Apoptosis and cell cycle arrest, and meanwhile induce Autophagy in MM cells in vitro. We further ascertained the role of Autophagy by using ATG5 siRNA or the Autophagy Inhibitor spautin-1, which partially reversed matrine's inhibitory effect on MM cells. Conversely, the combination of matrine with the Autophagy inducer rapamycin enhanced their anti-tumor activity. These findings suggest that Autophagy induced by matrine can lead to cell death in MM cells. Further mechanism investigation revealed that matrine treatment increased the levels of Reactive Oxygen Species (ROS) and AMPKα1 phosphorylation and decreased the phosphorylation of mTOR in MM cells. Additionally, co-treatment with AMPKα1 siRNA or the ROS scavenger N-acetyl-1-cysteine weakened the increase in Autophagy that was induced by matrine. Finally, we demonstrated a synergistic inhibitory effect of matrine and rapamycin against MM in a xenograft mouse model. Collectively, our findings provided novel insights into the anti-MM efficacy of matrine and suggest that matrine induces Autophagy by triggering ROS/AMPK/mTOR axis in MM cells, and combinatorial treatment of matrine and rapamycin may be a promising therapeutic strategy against MM.

Keywords

Apoptosis; Autophagy; Matrine; Multiple myeloma; Reactive oxygen species.

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