Juglone, a novel activator of ferroptosis, induces cell death in endometrial carcinoma Ishikawa cells.

Ferroptosis is a novel iron-dependent cell death pathway mainly caused by an abnormal redox state and associated with various diseases including cancer. Recently, much attention has been paid to natural compounds that are involved in its activation and inhibition. This is the first ever study to demonstrate the role of juglone isolated from Carya cathayensis green peel in inducing autophagy and inhibiting endometrial cancer (EC) cell migration. Subsequently, Fe2+ accumulation, lipid peroxidation, GSH depletion, the upregulation of HMOX1, and heme degradation to Fe2+ were reported. Juglone was involved in inducing autophagy and inhibiting cell migration and endoplasmic reticulum stress, which are the new hallmarks of cancer treatment. Collectively, our data indicate that juglone as a functional food ingredient induces the programmed cell death of EC cells by activating oxidative stress and suggest a novel therapeutic approach for the treatment and prevention of EC.