High-copper overload induces cuproptosis-like mitochondrial dysfunction and ferroptosis-associated oxidative stress in endometrial cancer cells

Endometrial cancer is a prevalent gynecological malignancy in women, which notably impacts the global female reproductive system. Given the challenges posed by tumor recurrence, metastasis, and drug resistance in the treatment of endometrial cancer (EC), there is a compelling need to explore experimental models. In this investigation, we evaluated the cellular effects of high-copper overload in EC cells and examined its association with mitochondrial metabolic disturbance and ferroptosis-associated oxidative stress. The analysis focused on the association between high-copper overload and cell death pathways through disruptions in ion homeostasis. The findings revealed that high-copper overload impeded the proliferation and migration of EC cells and was accompanied by increased cell death. Additionally, we observed that high-copper overload was associated with ferroptosis-related changes, influencing mitochondrial-associated metabolic markers. The data obtained in this study suggest that high-copper overload is associated with cuproptosis-like mitochondrial dysfunction and ferroptosis-associated oxidative stress in EC cells, thereby providing preliminary experimental evidence for further mechanistic investigation.