Nano-Pt induced mitochondria-dependent apoptosis and cytoprotective autophagy in human NSCLC cells
Jie Wu1, Xin Huang2, Zhongqing Xiao3
1Department of Respiratory and Critical Care Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450055, China.
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.
Insights
Amine-caged platinum nanoclusters (Nano-Pt) effectively combat non-small cell lung cancer (NSCLC) by inhibiting viability, promoting apoptosis, and causing DNA damage. Nano-Pt
Area of Science:
- Nanomedicine
- Oncology
- Cell Biology
Background:
- Classical chemotherapy for non-small cell lung cancer (NSCLC) has limitations, including poor efficacy and severe side effects.
- Platinum nanomaterials (Pt-NMs) show promise as alternative antitumor agents, but their mechanisms in NSCLC are not fully understood.
- The interplay between Pt-NMs, autophagy, and apoptosis in NSCLC remains an underexplored area.
Purpose of the Study:
- To investigate the anti-NSCLC effects of amine-caged platinum nanoclusters (Nano-Pt).
- To elucidate the molecular mechanisms of Nano-Pt action, including its impact on cell cycle, migration, proliferation, and apoptosis.
- To explore the interaction between Nano-Pt and autophagy in NSCLC cells.
Main Methods:
- Utilized cell cycle, migration, proliferation, apoptosis, and autophagy assays to evaluate Nano-Pt effects.
- Assessed DNA damage, mitochondrial membrane potential (MMP), and permeability transition.
- Analyzed the expression of apoptosis-related proteins (Bax, PARP) and the role of autophagy inhibitors.
Main Results:
- Nano-Pt significantly inhibited NSCLC cell viability and migration.
- Nano-Pt induced S phase arrest, DNA damage, and apoptosis by reducing MMP and increasing permeability transition.
- Apoptosis was mediated by upregulation of Bax and PARP, and accompanied by protective autophagy that could be enhanced by inhibitors.
Conclusions:
- Amine-caged Pt nanoclusters demonstrate significant anti-NSCLC activity.
- Nano-Pt exerts its effects through DNA damage, cell cycle arrest, and apoptosis induction, modulated by mitochondrial pathways.
- The findings clarify the molecular mechanisms of Nano-Pt in NSCLC and highlight its potential as a novel platinum-based chemotherapy drug with improved efficacy and reduced side effects.
Related Concept Videos
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
01:31The Intrinsic Apoptotic Pathway
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...