Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation

著者: Cong Zhou, Ting Yu, Rui Zhu, Junjie Lu, Xiaohu Ouyang, Zili Zhang, Qianyun Chen, Junyi Li, Jing Cui, Feng Jiang, Kim Yun Jin, Alexey Sarapultsev, Fangfei Li, Ge Zhang, Shanshan Luo, Desheng Hu - International Journal of Biological Sciences 2023 被引用: 166

ubiquitination assay. In addition, Tim-AIII inhibited cell proliferation, induced cell death, led to ROS and iron accumulation, MDA production, GSH depletion, as well as GPX4 ubiquitination and degradation, were markedly abrogated when HSP90 was knockdown by HSP90-shRNA transfection. Importantly, Tim-AIII also showed a strong capacity of preventing tumor growth by promoting ferroptosis in a subcutaneous xenograft tumor model, whether C57BL/6J or BALB/c-nu/nu nude mice. Together, HSP90 was identified as a new target of Tim-AIII. Tim-AIII, by binding and forming a complex with HSP90, further targeted and degraded GPX4, ultimately induced ferroptosis in NSCLC. These findings provided solid evidence that Tim-AIII can serve as a potential candidate for NSCLC treatment.