Work

Curcumin analogues trigger heme oxygenase-1-mediated ferroptosis to halt endometrial cancer growth

Year: 2026

Type: article

Abstract: Background: Advanced endometrial cancer remains challenging to treat due to limited therapeutic options and drug resistance. Ferroptosis, an iron-dependent form of cell death, offers a potential strategy for overcoming resistance. Curcumin analogues with improved bioavailability, such as HO-3867 and AKT-100, exhibit potent anti-cancer activity, but their mechanisms remain under-explored. Methods: KLE, Hec50co and Ishikawa endometrial cancer cells were treated with HO-3867 or AKT-100. RNA sequencing, qPCR, and immunoblotting assessed ferroptosis-related gene expression, focusing on HMOX1. Intracellular iron and ROS were measured via FerroOrange and DCFH-DA staining. Cytotoxicity and colony formation were evaluated using CyQUANT assays, with pharmacological inhibitors (ZnPP, Liproxstatin-1, Z-VAD-FMK) and HMOX1 siRNA to dissect the roles of ferroptosis and apoptosis. Results: Both analogues upregulated multiple ferroptosis genes, prominently HMOX1. AKT-100 increased intracellular iron and ROS levels. Inhibition of HMOX1, ferroptosis, or apoptosis partially rescued cell viability, while HMOX1 knockdown enhanced clonogenic growth, confirming its key role in AKT-100-mediated cytotoxicity. Conclusions: studies targeting HMOX1 in endometrial cancer.

Source: Cell Death

DOI: 10.1016/j.celld.2026.100015