2-B-YIA6-3 〇安曇 麻奈¹、吉江 幹浩¹、草間 和哉¹、中野 沙耶¹、津留 涼也¹、加藤 友康^1,2、田村 和広¹ Mana Azumi¹, Mikihiro Yoshie¹, Kazuya Kusama¹, Saya Nakano¹, Atsuya Tsuru¹, Tomoyasu Kato^1,2, Kazuhiro Tamura^{1 1}東京薬科大・薬・内分泌薬理、²国立がん研究センター中央病院・婦人腫瘍科 ¹Dept. Endocrine Pharmacol. Tokyo Univ. Pharmacy and Life Sci., ²Div. Gynecol., Natl. Cancer Ctr. Hosp. Ovarian cancer is a gynecologic malignancy with a high mortality rate. Eribulin, a non-taxane microtubule inhibitor approved for breast cancer and sarcoma, exerts antitumor efficacy in ovarian cancer cells (author et al, BPB. 2022:45). Ferroptosis, an iron-dependent cell death resulting from lipid peroxidation, is triggered by an accumulation of intracellular iron leading to oxidative stress. Reactive oxygen species (ROS) are a　cause of oxidative stress, and crucial for mitochondrial homeostasis. We explored the involvement of　ferroptosis and its mechanism in the antitumor activity of eribulin in ovarian cancer cells (RMG-1). Eribulin-induced cell death was mitigated by deferoxamine, an iron chelator. Eribulin elevated the levels of　intracellular iron, lipid peroxides, ROS, and mitochondrial membrane potential. Eribulin downregulated NRF2, heme oxygenase-1 (HO-1) and dihydroorotate dehydrogenase (DHODH), whereas glutathione peroxidase (GPX4) protein level remained unaffected. Combining eribulin with ML210, a GPX4-inhibiting ferroptosis inducer, enhanced eribulin-induced cell death. Taken together, eribulin triggers ferroptosis characterized by increased intracellular iron, lipid peroxidation, and ROS in ovarian cancer cells. The ferroptosis-inducing effect may be orchestrated through suppression of the NRF2/HO-1 signaling pathway and lipid peroxidation inhibition by DHODH. These findings illuminate the potential of eribulin-induced ferroptosis as a therapeutic strategy in ovarian cancer treatment.