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

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.

SUBMITTER: Ning N

PROVIDER: S-EPMC10716160 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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

Ning Nannan N Shang Ziqi Z Liu Zhiping Z Xia Zhizhou Z Li Yang Y Ren Ruibao R Wang Hongmei H Zhang Yi Y

Cell death discovery 20231213 1

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 us ...[more]

PMID: 38086802

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Dataset Information

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

Publications

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

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