Scoparone induces mitophagy and apoptosis via ROS accumulation in pancreatic cancer cells

Pancreatic cancer (PC) is one of the deadliest malignancies worldwide. In the present study, we demonstrated that a traditional Chinese medicine extract monomer, scoparone (Scop), significantly inhibited the growth of PC cells both in vitro and in vivo. Further studies revealed that Scop could induce PINK1/Parkin-mediated mitophagy and apoptosis in PC cells; thus, inhibition of mitophagy could alleviate the anti-PC effect and apoptosis of Scop. Mechanistically, Scop exerts its anti-PC effects via the Akt/mTOR pathway. In addition, Scop increases the level of cellular reactive oxygen species (ROS) in PC cells, which may be a key factor, as the ROS inhibitor N-acetylcysteine significantly reversed the effects of mitophagy and apoptosis in PC cells. Our findings highlight Scop shows potential as a therapeutic lead candidate, offering novel insights into the antitumor potential of traditional Chinese medicine. This study elucidates the critical role of Scop in regulating mitophagy and apoptosis in PC cells, providing a foundation for future therapeutic development.