Mitochondrial impairment and downregulation of Drp1 phosphorylation underlie the antiproliferative and proapoptotic effects of alantolactone on oral squamous cell carcinoma cells

作者：Yafei Zhang, Bingqian Yang, Chengwei Tu, Yifan Ping, Shuhong Chen, Tong Wu, Zheyu Zhao, Yixin Mao, Zhan Yang, Zelin Cao, Jianmin Li, Kate Huang, Xi Ding, Gang Wu, Peng Zou, Zhennan Deng, Xiaoyu Sun · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-04188-2 · 被引用次数：26 · 研究领域：Mitochondrial Function and Pathology、Coenzyme Q10 studies and effects、Cell death mechanisms and regulation

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent and fatal oral cancers. Mitochondria-targeting therapies represent promising strategies against various cancers, but their applications in treating OSCC are limited. Alantolactone (ALT) possesses anticancer properties and also regulates mitochondrial events. In this study, we explored the effects of ALT on OSCC and the related mechanisms. METHODS: The OSCC cells were treated with varying concentrations and duration of ALT and N-Acetyl-L-cysteine (NAC). The cell viability and colony formation were assessed. The apoptotic rate was evaluated by flow cytometry with Annexin V-FITC/PI double staining. We used DCFH-DA and flow cytometry to detect reactive oxygen species (ROS) production and DAF-FM DA to investigate reactive nitrogen species (RNS) level. Mitochondrial function was reflected by mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. KEGG enrichment analyses determined the mitochondrial-related hub genes involved in OSCC progression. Dynamin-related protein 1 (Drp1) overexpression plasmids were further transfected into the cells to analyze the role of Drp1 in OSCC progression. Immunohistochemistry staining and western blot verified the expression of the protein. RESULTS: ALT exerted anti-proliferative and pro-apoptosis effects on OSCC cells. Mechanistically, ALT elicited cell injury by promoting ROS production, mitochondrial membrane depolarization,...