New Platinum(II) agent induces bimodal death of apoptosis and autophagy against A549 cancer cell.

Agents with multiple modes of tumor cell death can be effective chemotherapeutic drugs. One example of a bimodal chemotherapeutic approach is an agent that can induce both apoptosis and autophagic death. Thus far, no clinical anticancer drug has been shown to simultaneously induce both these pathways. Mono-functional platinum complexes are potent anticancer drug candidates which act through mechanisms distinct from cisplatin. Here, we describe the synthesis and characterize of two mono-functional platinum complexes containing 8-substituted quinoline derivatives as ligands. In comparison to cisplatin, n-Mon-Pt-1 exhibited a greater in vitro cytotoxicity, was more effective in resistant cells and elicited a better anticancer effect. Mechanistic experiments indicate that n-Mon-Pt-1 mainly accumulates in mitochondria, and stimulates significant TrxR inhibition, ROS release and an ER stress response, ultimately resulting in a simultaneous induction of apoptosis and autophagy. Importantly, compared to cisplatin, n-Mon-Pt-1 exhibits lower acute toxicity and better anticancer activity in a murine tumor model.