Inducing Ferroptosis Shows Exquisite Sensitivity Against Adrenocortical Carcinomas

Adrenocortical carcinoma (ACC) is a rare and highly aggressive cancer originating in the adrenal glands, often diagnosed at advanced stages with a poor prognosis. Current treatment options for ACC are limited and often ineffective, highlighting an urgent need for novel therapeutic strategies. This study addresses the critical knowledge gap regarding alternative, targeted approaches to combat ACC progression and improve patient outcomes.

The study revealed that adrenocortical carcinoma cells exhibited remarkable sensitivity to ferroptosis induction. In vitro experiments showed that erastin treatment at 5 µM for 48 hours resulted in a significant reduction in cell viability, leading to 85% cell death compared to untreated controls (p<0.001). Similarly, RSL3 induced 78% cell death at 0.1 µM within 24 hours. This sensitivity was confirmed by a 2.5-fold increase in lipid peroxidation markers, indicating active ferroptosis. The most striking finding was in the in vivo model, where daily administration of erastin (10 mg/kg) led to a 60% reduction in tumor volume in ACC xenografts compared to vehicle-treated controls (p<0.001) over 21 days, without significant systemic toxicity. Furthermore, immunohistochemical analysis of tumor tissues showed a 3-fold increase in ferroptotic markers in the treated group.