Cucurbitacin E elicits apoptosis in laryngeal squamous cell carcinoma by enhancing reactive oxygen species-regulated mitochondrial dysfunction and endoplasmic reticulum stress

. Further investigations indicated that CuE significantly decreased mitochondrial membrane potential, thereby promoting cytochrome c release, increasing cleaved-Caspase 3 and cleaved-PARP levels, and triggering mitochondria-dependent apoptosis. Concurrently, exposure of LSCC cells to CuE enhanced endoplasmic reticulum (ER) stress, mobilized the protein kinase RNA-like endoplasmic reticulum kinase/initiation factor 2a/ATF4/C-EBP homologous protein pathway, and induced LSCC cell apoptosis. Finally, CuE markedly elevated intracellular reactive oxygen species (ROS) levels. When ROS were eliminated with N-acetylcysteine, CuE-mediated mitochondrial dysfunction, ER stress, and cell apoptosis were nearly abolished. Similar outcomes were observed in murine LSCC models. Together, these results highlight that CuE suppresses proliferation while triggering apoptosis in LSCC cells via ROS-regulated mitochondrial dysfunction and the ER stress pathway. Hence, CuE may serve as a promising candidate for LCSS treatment.