文献类型：期刊文献

英文题名：Curdepsidone A Induces Intrinsic Apoptosis and Inhibits Protective Autophagy via the ROS/PI3K/AKT Signaling Pathway in HeLa Cells

作者：Xu, Sunjie[1];Li, Zhimin[1];Xin, Xiujuan[1];An, Faliang[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[2]Marine Biomed Sci & Technol Innovat Platform Lin G, 4,Lane 218,Haiji Sixth Rd, Shanghai 201306, Peoples R China

年份：2024

卷号：22

期号：5

外文期刊名：MARINE DRUGS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001232877000001)】；

基金：We sincerely thank Xigao Liu and his student Wenxu Ma of Qilu Hospital of Shandong University for providing a variety of tumor cell lines and technical guidance for this work. This work was also supported by the Open Research Fund Program of the State Key Laboratory of Bioreactor Engineering and the Shanghai Collaborative Innovation Center for Biomanufacturing Technology.

语种：英文

外文关键词：curdepsidone A; HeLa cells; anti-tumor activity; ROS; PI3K/AKT signaling pathway

摘要：Among female oncology patients, cervical cancer stands as the fourth most prevalent malignancy, exerting significant impacts on their health. Over 600,000 women received the diagnosis of cervical cancer in 2020, and the illness claimed over 300,000 lives globally. Curdepsidone A, a derivative of depsidone, was isolated from the secondary metabolites of Curvularia sp. IFB-Z10. In this study, we revised the molecular structure of curdepsidone A and investigated the fundamental mechanism of the anti-tumor activity of curdepsidone A in HeLa cells for the first time. The results demonstrated that curdepsidone A caused G0/G1 phase arrest, triggered apoptosis via a mitochondrial apoptotic pathway, blocked the autophagic flux, suppressed the PI3K/AKT pathway, and increased the accumulation of reactive oxygen species (ROS) in HeLa cells. Furthermore, the PI3K inhibitor (LY294002) promoted apoptosis induced by curdepsidone A, while the PI3K agonist (IGF-1) eliminated such an effect. ROS scavenger (NAC) reduced curdepsidone A-induced cell apoptosis and the suppression of autophagy and the PI3K/AKT pathway. In conclusion, our results revealed that curdepsidone A hindered cell growth by causing cell cycle arrest, and promoted cell apoptosis by inhibiting autophagy and the ROS-mediated PI3K/AKT pathway. This study provides a molecular basis for the development of curdepsidone A as a new chemotherapy drug for cervical cancer.