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EP992 Iron-dependent cell death ‘ferroptosis’ is a new therapeutic strategy for ovarian cancer
  1. M Takenaka1,
  2. T Furui1,
  3. N Suzuki1,
  4. T Koike1,
  5. H Aoki1,
  6. H Nagasawa2 and
  7. K-I Morishige1
  1. 1Gifu University Hospital
  2. 2Gifu Pharmaceutical University, Gifu, Japan


Introduction/Background Chemo-resistant ovarian cancer is a highly fatal disease and a new strategy is necessary to improve the prognosis. The oncogenic lethal small molecule erastin triggers a unique iron-dependent form of cell death termed ‘ferroptosis’. This new type of programmed cell death (PCD) is expected to induce eradication of chemotherapeutic resistant cancer cells. We demonstrated this new form of cell death in ovarian cancer cells.

Methodology The epithelial ovarian cancer cell lines were treated with erastin, cisplatin (CDDP) and deferoxamine (DFO). Cell viability, glutathione (GSH) concentrations and whole (cytosolic and lipid) ROS production were assessed. The expression of protein markers for other types of PCD was identified by using western blotting.

Results TOV-21G cells were the most sensitive to erastin among four ovarian cancer cell lines. The sensitivity to erastin was moderate in SKOV3ip1 cells, and resistant in CaOV3 and KOC-7C cells. DFO rescued growth inhibition induced by erastin. Erastin reduced intracellular GSH level, resulting in increase of whole ROS in TOV-21G cells. The basal GSH level was lower and the basal ROS level was higher in TOV-21G cells than KOC-7C cells. The expression of protein markers for apoptosis, necrosis and autophagy were not changed by erastin. Growth inhibition induced by CDDP was not rescued by DFO. A low-dose erastin combined with CDDP remarkably inhibited cell growth in TOV-21G cells.

Conclusion Erastin induced ferroptosis in ovarian cancear cells of which intracellular GSH level was low. Ferroptosis had great potential to become a new approach in chemotherapies of ovarian cancer.

Disclosure Nothing to disclose.

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