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

Year: 2026

Type: article

Abstract: This study investigated the ability of the bioavailable curcumin analogues HO‑3867 and AKT‑100 to induce ferroptosis and apoptosis in endometrial cancer cells, with emphasis on the mechanistic role of heme oxygenase‑1 (HMOX1). Human endometrial cancer cell lines were treated with either compound, and ferroptosis‑related gene expression was evaluated by RNA sequencing, qPCR, and immunoblotting. Intracellular iron and reactive oxygen species (ROS) accumulation were quantified using FerroOrange and DCFH‑DA staining, respectively. Apoptosis was assessed by caspase 3/7 activity, while cell viability and clonogenic capacity were evaluated using CyQUANT and colony‑formation assays. Pharmacologic inhibitors of HMOX1, ferroptosis, and apoptosis, along with HMOX1 siRNA, were used to define pathway contributions. Both agents dysregulated ferroptosis‑associated genes, with HMOX1 showing the strongest induction. AKT‑100 markedly increased intracellular iron and ROS levels, as well as caspase 3/7 activity, and inhibition of HMOX1, ferroptosis, or apoptosis partially rescued cell survival. HMOX1 knockdown enhanced clonogenic growth, confirming its central role in AKT‑100–mediated cytotoxicity. These findings demonstrate that HO‑3867 and AKT‑100 inhibit endometrial cancer cell growth by activating HMOX1‑driven ferroptosis and apoptosis, supporting further in vivo evaluation of HMOX1‑targeted therapies.

Source: Cell Death

DOI: 10.1016/j.celld.2026.100015