The potential of vitamin K₃ as an anticancer agent against breast cancer that acts via the mitochondria-related apoptotic pathway

Purpose: We tried to clarify the cytotoxic mechanism of VK₃ using the breast cancer cell line MCF-7. Methods: Cytotoxicity was measured via intracellular esterase activity. DNA fragmentation was assessed by agarose gel electrophoresis. JC-1 staining was applied to measure mitochondrial dysfunction. Caspase activation and reactive oxidative species (ROS) generation were also measured. Results: VK₃ exhibited cytotoxicity that caused DNA fragmentation in MCF-7 cells with an IC₅₀ of 14.2 μM. JC-1 staining revealed that VK₃ caused mitochondrial dysfunction including a disappearance of mitochondrial membrane potential. Additional investigation showed that the mitochondrial damage was induced by the generation of ROS and the subsequent activation of caspase-7 and -9. Conclusions: Our findings demonstrate that VK₃-induced apoptosis is selectively initiated by the mitochondria-related pathway and might be useful in breast cancer chemotherapy.