High selectivity and significant cytotoxicity of rare earth naphthalene dicarboxylate complexes on non-small cell lung cancer cells

Abstract

Functional 1,8-naphthalimide derivatives are rapidly developing in the field of anticancer research. However, the unpredictable side effects of 1,8-naphthalimide derivatives limit their transition from clinical trials to clinical drugs. To low down the overall cytotoxicity of 1,8-naphthalimide derivatives after coordination with metals, we have synthesized and characterized three new rare earth naphthalene dicarboxylate complexes with the general molecular formula of [Ln(TTA)3NI-Phen], where Ln=Er, Nd, Yb, respectively. In vitro antitumor screening revealed that all three complexes exhibit better inhibitory activities against A549 and H1299 cancer cell lines compared with the commercial anticancer drug cisplatin. Especially, Er(TTA)3NI-Phen exhibited specific cytotoxicity to H1299 cancer cells in micromole magnitude and lower toxicity to normal human cells Beas-2b. Interestingly, Er(TTA)3NI-Phen triggers lung cancer cells apoptosis via a mitochondrial dysfunction pathway, which is caused by dysfunction of mitochondria and cell cycle arrest. Most importantly, Er(TTA)3NI-Phen demonstrates an inhibition rate of up to 84% against H1299 tumors.