在女性肿瘤患者中，宫颈癌是第四大常见恶性肿瘤，对她们的健康产生重大影响。 2020 年，超过 60 万名女性被诊断出患有宫颈癌，该疾病在全球夺去了超过 30 万人的生命。 Curdepsidone A 是一种 depsidone 衍生物，是从 Curvularia sp. 的次生代谢产物中分离出来的。 IFB-Z10。在本研究中，我们对curdepsidone A的分子结构进行了修改，并首次研究了curdepsidone A在HeLa细胞中抗肿瘤活性的基本机制。结果表明，curdepsidone A 引起 G0/G1 期阻滞，通过线粒体凋亡途径引发细胞凋亡，阻断自噬流，抑制 PI3K/AKT 途径，并增加 HeLa 细胞中活性氧 (ROS) 的积累。此外，PI3K抑制剂（LY294002）促进curdepsidone A诱导的细胞凋亡，而PI3K激动剂（IGF-1）消除了这种作用。 ROS 清除剂 (NAC) 可减少 curdepsidone A 诱导的细胞凋亡以及自噬和 PI3K/AKT 通路的抑制。总之，我们的结果表明，curdepsidone A 通过引起细胞周期停滞来阻碍细胞生长，并通过抑制自噬和 ROS 介导的 PI3K/AKT 途径促进细胞凋亡。该研究为curdepsidone A作为宫颈癌新型化疗药物的开发提供了分子基础。

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.