2. Academic Validation
  3. Trifluoperazine activates AMPK / mTOR / ULK1 signaling pathway to induce mitophagy in osteosarcoma cells

Trifluoperazine activates AMPK / mTOR / ULK1 signaling pathway to induce mitophagy in osteosarcoma cells

  • Chem Biol Interact. 2024 Feb 13:110904. doi: 10.1016/j.cbi.2024.110904.
Wenhui Shen 1,  Xianhui Zeng 2,  Xiangchen Zeng 3,  Baoshan Hu 4,  Chong Ren 5,  Zhiming Lin 4,  Long Zhang 3,  Gang Rui 4,  Miersalijiang Yasen 6,  Xiaohui Chen 7
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, 361000, China.
  • 2 Department of Infectious Diseases, Hainan Women and Children's Medical Center, Hainan Medical University, Haikou, 570206, China.
  • 3 State Key Laboratory of Cellular Stress Biology, School of Medicine, Xiamen University, Xiamen, 361102, China.
  • 4 Department of Orthopedic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361001, China.
  • 5 Department of Basic Medical Sciences, School of Medicine, Xiamen University, Xiamen, 361102, China.
  • 6 Department of Orthopedic Surgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, 361000, China. Electronic address: mi.yasen@zsxmhospital.com.
  • 7 State Key Laboratory of Cellular Stress Biology, School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Orthopedic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361001, China. Electronic address: chenxiaohui@xmu.edu.cn.
PMID: 38360085 DOI: 10.1016/j.cbi.2024.110904
Abstract

Osteosarcoma is a prevalent kind of primary bone malignancy. Trifluoperazine, as an antipsychotic drug, has anti-tumor activity against a variety of cancers. Nevertheless, the impact of trifluoperazine on osteosarcoma is unclear. Our investigation aimed to explore the mechanism of trifluoperazine's effect on osteosarcoma. We found that trifluoperazine inhibited 143B and U2-OS osteosarcoma cell proliferation in a method based on the dose. Furthermore, it was shown that trifluoperazine induced the accumulation of Reactive Oxygen Species (ROS) to cause mitochondrial damage and induced Mitophagy in osteosarcoma cells. Finally, combined with RNA-seq results, we first demonstrated the AMPK/mTOR/ULK1 signaling pathway as a potential mechanism of trifluoperazine-mediated Mitophagy in osteosarcoma cells and can be suppressed by AMPK Inhibitor Compound C.

Keywords

AMPK; Mitophagy; Osteosarcoma; Trifluoperazine; ULK1; mTOR.

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