3,6-环末[二氧]基-1,10-双伯大蒿甾烯（EDBD）是一种从可食用野生植物中分离出的内过氧化物化合物，通过减少GPX4和谷胱甘肽的表达，在HL-60细胞中诱导了依赖铁的类铁死亡。相反，磺胺嘧啶（SSZ）是一种临床使用的抗炎药物，通过系统xc-诱导铁死亡。本研究中，我们调查了这两种化合物对三种人类乳腺癌细胞系（HBC-5，MCF-7和MDA-MB-231）的协同效应。EDBD诱导的细胞死亡被脂质过氧化抑制剂ferrostatin-1和铁螯合剂去铁胺甲磺酸盐所减轻，表明EDBD诱导了类铁死亡。此外，EDBD和SSZ的联合治疗在所有三个细胞系中协同诱导了细胞死亡。由于联合治疗的细胞毒性受到去铁胺甲磺酸盐和ferrostatin-1的抑制，EDBD和磺胺嘧啶的联合诱导了铁死亡。总的来说，EDBD增强了作为临床抗炎和抗癌药物候选物的SSZ的效果。©The Author(s) 2023. 由牛津大学出版社代表日本生物科学，生物技术和农化学学会出版。

3,6-Epidioxy-1,10-bisaboladiene (EDBD) is an endoperoxide compound isolated from edible wild plants that induces iron-dependent ferroptosis-like cell death in HL-60 cells by decreasing the expression of GPX4 and glutathione. In contrast, sulfasalazine (SSZ), a clinically used anti-inflammatory drug, induces ferroptosis through the system xc-. In this study, we investigated the synergistic effects of these two compounds on three human breast cancer cell lines (HBC-5, MCF-7, and MDA-MB-231). EDBD-induced cell death was relieved by the lipid peroxidation inhibitor ferrostatin-1 and the iron chelator deferoxamine mesylate indicating that EDBD induced ferroptosis-like cell death. Moreover, cotreatment with EDBD and SSZ synergistically induced cell death in all three cell lines. Because the cytotoxicity of the cotreatment was inhibited by deferoxamine mesylate and ferrostatin-1, the combination of EDBD and sulfasalazine synergistically induced ferroptosis. Collectively, EDBD enhanced the effects of SSZ as a clinical anti-inflammatory and anticancer drug candidate.© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.