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Cell Toxicity and Autophagy in A549 Cells Treated With Surface-Functionalized Graphene Derivatives.
Tae Yun Park1, Soo Young Kim2, Chang Seok Park3
1Division of Respiratory and Critical Care, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea.
Journal of Applied Toxicology : JAT
|September 9, 2025
Summary
Graphene oxide and its derivatives show concentration-dependent toxicity in lung cancer cells, with functionalized forms being more toxic. Graphene exposure increases autophagy activity through a beclin-1-independent pathway, suggesting complex intracellular mechanisms require further study.
Area of Science:
- Nanomaterials Science
- Cell Biology
- Toxicology
Background:
- Graphene oxide (GO) and its derivatives possess unique properties, leading to diverse applications.
- However, their biological impacts and intracellular toxicity mechanisms remain incompletely understood.
- Investigating these effects is crucial for safe application of graphene-based materials.
Purpose of the Study:
- To investigate the cytotoxic and autophagic activities of graphene oxide (GO) and its derivatives.
- To examine the effects of GO, dodecylamine-oxidized graphene (DA-GO), reduced graphene oxide (rGO), and sodium dodecyl sulfate-reduced graphene oxide (SDS-rGO) on A549 human lung carcinoma cells.
- To elucidate the intracellular mechanisms underlying graphene-induced cellular responses.
Main Methods:
- A549 human lung carcinoma cells were treated with varying concentrations of different graphene materials.
- Cytotoxicity was assessed by measuring cell viability and protein expression levels.
- Autophagy activity was evaluated by monitoring the conversion of LC3A/B-I to LC3A/B-II and measuring levels of mTOR and beclin-1 proteins.
Main Results:
- Graphene exposure induced a concentration-dependent toxic effect in A549 cells, with significant toxicity observed at concentrations above 100 µg/mL.
- Functionalized graphene derivatives (DA-GO and SDS-rGO) exhibited higher toxicity compared to native GO at high concentrations.
- Increased autophagy activity was indicated by elevated LC3A/B-II levels and reduced mTOR protein expression across all tested graphene types.
- Beclin-1 levels were decreased for all GO types, suggesting a beclin-1-independent autophagy induction.
Conclusions:
- Graphene oxide and its derivatives exert concentration-dependent cytotoxicity on lung carcinoma cells.
- Functionalization of graphene materials can significantly enhance their toxicity.
- Graphene exposure appears to trigger autophagy through a noncanonical, beclin-1-independent pathway.
- Further research is necessary to fully understand the complex mechanisms of graphene-induced autophagy and potential involvement of apoptosis-related pathways.
