高级别浆液性卵巢癌（HGSOC）是最常见和致命的卵巢癌组织型。缺乏早期检测方法、有限的治疗药物和低的5年生存率反映了开发新疗法的紧迫需求。ε菌酮（eupenifeldin）是一种来自Brefeld单胞菌（Eupenicillium brefeldianum）的细胞毒真菌代谢产物。在三种HSGOC细胞系（OVCAR3、OVCAR5、OVCAR8）中，ε菌酮的IC50值小于10 nM，而非肿瘤性输卵管分泌上皮细胞系（FTSEC）需要10倍浓度的ε菌酮才能发生细胞毒性。空心纤维实验证明OVCAR3中有明显的细胞毒作用。ε菌酮显著增加了OVCAR3和-8的Annexin V染色，但不影响OVCAR5。ε菌酮激活了OVCAR3、OVCAR5和OVCAR8中的caspase 3/7，然而，PARP的裂解只在OVCAR3中检测到。对OVCAR3进行的定量蛋白质组学研究表明镁星症是最丰富的细胞死亡途径。然而，验证实验证实镁星症并不是ε菌酮的细胞毒机制的一部分。自噬流和LC3B斑点实验发现，ε菌酮在OVCAR3中显示出弱的自噬诱导作用。与巴菲霉素联合处理抑制了ε菌酮的毒性，支持自噬诱导对于ε菌酮的细胞毒机制的贡献。

High-grade serous ovarian cancer (HGSOC) is the most common and lethal ovarian cancer histotype. Lack of early detection methods, limited therapeutic agents, and low 5-year survival rate reflect the urgent need to develop new therapies. Eupenifeldin, a bistropolone, originally isolated from Eupenicillium brefeldianum, is a cytotoxic fungal metabolite. In three HSGOC cell lines (OVCAR3, OVCAR5, OVCAR8), eupenifeldin was found to have an IC50 value less than 10 nM, while 10 times higher concentrations were required for cytotoxicity in nontumorigenic fallopian tube secretory epithelial cell lines (FTSEC). An in vivo hollow fiber assay showed significant cytotoxicity in OVCAR3. Eupenifeldin significantly increased Annexin V staining in OVCAR3 and -8, but not OVCAR5. Eupenifeldin activated caspases 3/7 in OVCAR3, OVCAR5, and OVCAR8; however, cleaved PARP was only detected in OVCAR3. Quantitative proteomics performed on OVCAR3 implicated ferroptosis as the most enriched cell death pathway. However, validation experiments did not support ferroptosis as part of the cytotoxic mechanism of eupenifeldin. Autophagic flux and LC3B puncta assays found that eupenifeldin displayed weak autophagic induction in OVCAR3. Inhibition of autophagy by cotreatment with bafilomycin reduced the toxicity of eupenifeldin, supporting the idea that induction of autophagy contributes to the cytotoxic mechanism of eupenifeldin.