Nano-Pt induced mitochondria-dependent apoptosis and cytoprotective autophagy in human NSCLC cells

Abstract

Given that currently used classical chemotherapeutic drugs lack the ideal therapeutic effect and produce severe side effects, platinum nanomaterials (Pt-NMs) have gradually gained attention, and their antitumor effect has been initially explored. However, the specific mechanisms underlying the action of Pt-NMs in non–small cell lung cancer (NSCLC) cells remain unclear. Moreover, the interaction between Pt-NMs and autophagy in inducing apoptosis of NSCLC cells remains unexplored. In this study, we explored the anti-NSCLC effect of amine-caged Pt nanoclusters (Nano-Pt) using cell cycle, migration, proliferation, apoptosis, and autophagy assays. We found that Nano-Pt significantly inhibited cell viability, reduced migration ability, caused DNA damage, induced S phase (period of DNA synthesis in the cell cycle) arrest, and promoted apoptosis in NSCLC cells. Nano-Pt also reduced mitochondrial membrane potential (MMP), increased permeability transition, and promoted apoptosis by upregulating Bax and PARP expression. Nano-Pt-induced apoptosis was accompanied by protective autophagy, which could be enhanced by autophagy inhibitors. Our findings on the biological behavior and the interaction between autophagy and apoptosis can provide the clear anti-NSCLC molecular mechanism of Nano-Pt, which have a promising potential for the development of novel Pt-based antitumor chemotherapy drugs with excellent curative efficacy and fewer side effects.