Apoptosis and necroptosis-inducing effects of arctigenin on nasal septum carcinoma RPMI-2650 cells in 2D and 3D culture

Backgrounds Arctigenin derived from the seeds of Arctium lappa Linnaeus is known as an anticancer drug candidate by targeting various pathways involved in anticancer therapy. Methods Using 2D monolayer and 3D spheroid culture systems in nasal septum carcinoma RPMI-2650 cells, the effects of arctigenin and dexamethasone on cell viability, ROS levels, ATP level, mitochondrial function, apoptosis and necroptosis were examined. Results The combination treatment of both compounds induced strong cytotoxicity, accompanied by increases of sub-G 0 /G 1 peak, annexin V-PE-positive cells, and ROS levels, loss of mitochondrial membrane potential, and decrease of cellular ATP content. These changes were observed as simultaneous induction of DNA damage, apoptosis, and necroptosis. A series of changes by arctigenin and dexamethasone were efficiently restored by decreasing ROS levels or supplementing ATP. Treatment of 3D spheroids with arctigenin and dexamethasone decreased cell viability in the spheroids, but it was slightly resistant than cells under 2D conditions. In addition, this phenomenon was accompanied by an increase in mediators for both apoptosis and necroptosis. Conclusion Results of this study suggest that the apoptosis and necroptosis-inducing effects of arctigenin are associated with ATP depletion due to oxidative mitochondrial dysfunction.