The antitumor effects of mitochondria-targeted 6-(nicotinamide) methyl coumarin

Cancer is the second leading cause of death worldwide. Traditional antitumor drugs exhibit severe cytotoxic and side effects. Lung cancer needs new and more effective treatment approaches. Coumarin derivatives can act on various tumor cells and show anti-proliferative activity through various mechanisms, including mitochondrial signaling cascades that regulate development and apoptosis of cells. Mitochondria-targeted coumarin derivatives have not been reported yet. Taking advantage of the fact that cancer cells frequently have higher mitochondria membrane potential, we synthesized a mitochondria-targeted 6-(nicotinamide) methyl coumarin by coupling 6-methyl coumarin to nicotinamide. Our results demonstrate that 6-(nicotinamide) methyl coumarin preferentially kills A549 cells through inducing A549 cells apoptosis, mediated by increasing ROS level and causing mitochondrial depolarization. Strikingly, the viability of the A31 cells treated with 6-(nicotinamide) methyl coumarin did not decrease, indicating that 6-(nicotinamide) methyl coumarin preferentially accumulates in A549 cells and A549 cells are much more susceptible to 6-(nicotinamide) methyl coumarin treatment compared with A31 cells.