2. Academic Validation
  3. A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling

A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling

  • Cell Death Discov. 2023 Dec 13;9(1):453. doi: 10.1038/s41420-023-01713-6.
Nannan Ning 1 2,  Ziqi Shang 3,  Zhiping Liu 4,  Zhizhou Xia 5,  Yang Li 6,  Ruibao Ren 7 8,  Hongmei Wang 9,  Yi Zhang 10 11
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, China.
  • 2 Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan, China.
  • 3 Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 4 Center of Intelligent Medical Engineering, School of Control Science and Engineering, Shandong University, Jinan, China.
  • 5 Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 Graduate School of Advanced Science and Engineering, Hiroshima University, Hiroshima, Japan.
  • 7 International Center for Aging and Cancer, Department of Hematology of The First Affiliated Hospital, Hainan Medical University, Haikou, China. rbren@sjtu.edu.cn.
  • 8 Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. rbren@sjtu.edu.cn.
  • 9 Department of Pharmacology, School of Medicine, Southeast University, Nanjing, China. 101012573@seu.edu.cn.
  • 10 Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, China. yizhang@sdu.edu.cn.
  • 11 Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan, China. yizhang@sdu.edu.cn.
PMID: 38086802 DOI: 10.1038/s41420-023-01713-6
Abstract

MP-HJ-1b is a novel microtubule inhibitor that we designed and reported previously. Ferroptosis is a newly identified type of nonapoptotic cell death induced by ferrous catalysis and lipid peroxidation. Here, transcriptomics, proteomics, and molecular docking analyses were combined to explore the novel effects of MP-HJ-1b on tumors. Both omics analyses suggested that MP-HJ-1b affects ribosomes, and we confirmed that it inhibits the ribosomal component proteins RPL35 and MRPL28. Colchicine was used as an analog, and the results showed that MP-HJ-1b and colchicine increased Reactive Oxygen Species and malondialdehyde levels and decreased reduced glutathione levels, suggesting that they promoted Ferroptosis in HeLa cells. Specifically, MP-HJ-1b downregulated SLC7A11 and GPX4 to enhance the classical pathway of Ferroptosis, while colchicine upregulated LC3A/B-II and enhanced Autophagy. Clinically, the serum concentrations of ferrous ions, reduced glutathione, and Hcy were higher in cervical Cancer patients than in healthy individuals. ALT, AST, Cho, HDL-C, and LDL-C levels were decreased in the serum of patients. Our study expands understanding of the way MP-HJ-1b promotes cell death and enriches research on microtubule inhibitors in the Ferroptosis field.

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