Abstract 109P
Background
Ferroptosis is a form of regulated cell death characterized by iron dependency and accumulation of reactive oxygen species (ROS) and lipid peroxides (LPO). Acquired cisplatin resistance is a challenge in the effective treatment of advanced and relapsed ovarian cancers. We have previously demonstrated that the ferroptosis inducers erastin and RSL3 effectively trigger ferroptosis and synergistically enhance the cytotoxic effects of cisplatin in ovarian cancer cells. The objective of this study is to search for FDA-approved candidate drugs that can induce ferroptosis in ovarian cancer cells.
Methods
We evaluated the inhibitory effects of five candidate drugs (sorafenib, disulfiram/copper, sulfasalazine, artesunate, zalcitabine) on cell viability using CKK8 proliferation assay in both ferroptosis-sensitive (TU-OC-1 and OVCAR3) and ferroptosis-resistant (KF and KOC-7C) cell lines. To determine the nature of the induced cell death, we co-administered a combination of Ferrostatin-1 and z-vad-fmk, while measuring the levels of intracellular markers associated with ferroptosis, including ROS and LPO, following the administration of the candidate drugs.
Results
Sorafenib, disulfiram/copper, sulfasalazine, and artesunate significantly reduced the viability of ovarian cancer cells. Ferrostatin-1 but not z-vad-fmk cotreatment could rescue the cell death caused by artesunate in OVCAR-3 and TU-OC-1 cells. Moreover, artesunate treatment significantly upregulated intracellular ROS and LPO in TU-OC-1 cells. These suggested artesunate induces ferroptosis in the cells.
Conclusions
These findings underscore the capacity of artesunate to induce ferroptosis in ovarian cancer cells. Consequently, further investigations will focus on studying the synergistic effects of artesunate when combined with cisplatin, thus providing insights for future therapeutic strategies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Health and Medical Research Fund (HMRF), HK.
Disclosure
All authors have declared no conflicts of interest.