Abstract 1616: Artesunate-induced ferroptosis: A novel strategy to overcome chemoresistance in ovarian cancer

Abstract The high propensity of ovarian cancer to develop chemoresistance contributes to its generally poor prognosis. Therefore, novel therapeutic approaches tackling this issue are highly sought after. Ferroptosis is a form of cell death characterized by iron dependency, increased lipid peroxidation, and disrupted cellular membranes. Many studies suggest that ferroptosis plays a crucial role in tumor suppression, thus providing new opportunities for cancer therapy. Artesunate is a well-known anti-malarial agent that can induce ferroptosis in multiple cancer types. Here in this study, we aim to investigate the potential of artesunate to induce ferroptosis and to attenuate cisplatin resistance in ovarian cancer cells. Cell viability assays indicated that artesunate effectively induced cell death. Cell death caused by artesunate was partially mitigated by the ferroptosis inhibitor ferrostatin-1 and the autophagy inhibitor chloroquine, suggesting the cytotoxic effects of artesunate are mediated through induction of both ferroptosis and autophagic cell death. Moreover, artesunate treatment significantly increased levels of reactive oxygen species (ROS) and lipid peroxidation (LPO), which are key hallmarks of ferroptosis. Western blot analysis also demonstrated that artesunate altered the expression of protein markers associated with increased ferroptosis, autophagy, and apoptosis in a time-dependent manner, suggesting a complex interplay between different cell death pathways. Co-treatment of artesunate with sub-cytotoxic concentrations of cisplatin significantly reduced cell viability after 48 hours, whereas ferrostatin-1 co-treatment partially rescued cell death. The combined treatment also led to an upregulation of ROS and LPO levels. Results suggested artesunate may enhance the cytotoxic effects of cisplatin by promoting ferroptotic cell death. These findings highlight the potential of artesunate as a novel agent to combat ovarian cancer chemoresistance through induction of ferroptosis, thereby enhancing therapeutic efficacy in clinical settings. Citation Format: Yusanne Yung Sing Chan, Oscar Gee Wan Wong, Claire Ling Yang Cheung, Esther Shuk Ying Wong, Xu Cong, Annie Nga Yin Cheung. Artesunate-induced ferroptosis: A novel strategy to overcome chemoresistance in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1616.