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.

MP-HJ-1b是我们之前设计和报道的一种新型微管抑制剂。铁死亡是一种新发现的由亚铁催化和脂质过氧化诱导的非凋亡细胞死亡类型。在这里，转录组学、蛋白质组学和分子对接分析相结合，探索 MP-HJ-1b 对肿瘤的新作用。两项组学分析都表明 MP-HJ-1b 影响核糖体，并且我们证实它抑制核糖体成分蛋白 RPL35 和 MRPL28。使用秋水仙碱作为类似物，结果表明MP-HJ-1b和秋水仙碱增加了活性氧和丙二醛水平，降低了还原型谷胱甘肽水平，表明它们促进了HeLa细胞的铁死亡。具体而言，MP-HJ-1b 下调 SLC7A11 和 GPX4 以增强铁死亡的经典途径，而秋水仙碱则上调 LC3A/B-II 并增强自噬。临床上，宫颈癌患者血清亚铁离子、还原型谷胱甘肽、Hcy浓度均高于健康个体。患者血清中 ALT、AST、Cho、HDL-C 和 LDL-C 水平降低。我们的研究扩展了对 MP-HJ-1b 促进细胞死亡方式的理解，并丰富了铁死亡领域微管抑制剂的研究。