Chemodynamic therapy agents Cu(II) complexes of quinoline derivatives induced ER stress and mitochondria-mediated apoptosis in SK-OV-3cells.

Abstract

Three Cu(II) complexes of quinoline derivatives as cancer chemodynamic therapy agents were synthesized and characterized. These complexes were heavily taken up by cells and reacted with cellular glutathione (GSH) to reduce Cu2+ to Fenton-like Cu+, which catalyzed endogenous H2O2 to produce the highly toxic hydroxyl radicals (•OH) to kill cancer cells. Cu1 and Cu2 initiated CAT activity declines, mitochondrial membrane potential and ATP concentration decrease, mitochondrial Ca2+ overload and ER stress response, leading to cell cycle arrest in sub-G1 and cancer cell caspase-dependent apoptosis. On account of the high GSH and H2O2 specific properties of the tumor microenvironment, Cu1 and Cu2 exhibited higher invitro anticancer activity and lower toxicity to normal cells. Cu1 and Cu2 efficiently inhibited tumor growth in the SK-OV-3 xenograft mouse model without obvious systemic toxicity.