Dual-target platinum(IV) complexes exhibit antiproliferative activity through DNA damage and induce ER-stress-mediated apoptosis in A549 cells

Platinum(II)-based chemotherapeutics are commonly used to treat various types of solid tumors, such as lung cancers. However, these compounds can cause serious side effects, including nephrotoxicity and ototoxicity, which affect the quality of life of patients. In our work, four novel dual target platinum(IV) complexes were designed and synthesized. In vitro results indicated that the title platinum(IV) complexes exhibited effective antitumor activities against the tested cancer cells and had lower toxicity and resistance factors than oxaliplatin and cisplatin. Further mechanistic experiments demonstrated that complex 11 accumulated in mitochondria and induced an elevation in ROS and an ER stress response via mitochondrial dysfunction. Notably, complex 11 significantly modulated the expression levels of proapoptosis proteins including cleaved-Caspase-3, Bax, and p53, and decreased the level of the prosurvival protein Bcl-2. Together, these results suggested that complex 11 might be a potential lead compound for future cancer therapy due to its potency and selectivity.

Automated summary

Novel dual target platinum(IV) complexes showed effective antitumor activities with lower toxicity and resistance factors than standard platinum-based chemotherapeutics, by modulating proapoptosis and prosurvival protein expression levels in cancer cells through mitochondrial dysfunction-induced mechanisms. Compound 11 has the potential to be a lead compound for future cancer therapy due to its potency and selectivity.