Scoparone induces both apoptosis and ferroptosis via multiple mechanisms in non-small-cell lung cancer cells.

ABSTRACT

The present study investigated the anti-tumour effects of scoparone, also known as 6,7-dimethoxycoumarin, in non-small-cell-lung cancer (NSCLC) cells. It was discovered that scoparone inhibited the proliferation and induced cell death of NSCLC cells. Scoparone induced both apoptosis and ferroptosis in NSCLC cells. Mechanically, scoparone treatment led to the FBW7-mediated ubiquitination and downregulation of Mcl-1. Moreover, scopaone induced Bax activation in a reactive oxygen species (ROS)-dependent manner. Interestingly, scoparone also triggered ferroptosis, a novel form of cell death, as evidenced by upregulation of lipid peroxidation, ROS, and iron levels. The mechanism investigation showed that scoparone activated the ROS/JNK/SP1/ACSL4 axis to trigger ferroptosis in NSCLC cells. Overall, our data suggest that scoparone is a promising agent for the treatment of NSCLC.