Blue LED causes autophagic cell death in human osteosarcoma by increasing ROS generation and dephosphorylating EGFR
Mingyu He1, Gege Yan1, Yang Wang2,3
1Department of Pharmacology, College of Pharmacy (The Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), Harbin Medical University, Harbin, China.
Abstract:
Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light-emitting diodes (LED)-based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation-induced autophagy characterized by alterations in autophagy protein markers including Beclin-1, LC3-II/LC3-I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti-tumour activities of blue LED irradiation. Next, ROS scavenger N-acetyl-L-cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED-induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin-1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin-1 and EGFR-immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin-1 upon blue LED irradiation in OS cells. In addition, Beclin-1 down-regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti-tumour effects on OS by triggering ROS and EGFR/Beclin-1-mediated autophagy signalling pathway, representing a potential approach for human OS treatment.
Insights
Blue LED irradiation effectively inhibits osteosarcoma cell growth by increasing reactive oxygen species (ROS) and activating autophagy. This novel therapeutic approach targets the EGFR/Beclin-1 pathway for potential human osteosarcoma treatment.
Area of Science:
- Oncology
- Biomedical Engineering
- Cell Biology
Background:
- Osteosarcoma (OS) is the most common primary bone cancer in adolescents.
- Light-emitting diode (LED) therapy shows promise for various diseases, but its effect on human OS is unexplored.
Purpose of the Study:
- To investigate the anti-tumour effects of blue LED irradiation on human osteosarcoma cells.
- To elucidate the underlying molecular mechanisms, including reactive oxygen species (ROS) production and autophagy signaling.
Main Methods:
- Human OS cells were exposed to blue LED irradiation.
- Assessed cell proliferation, migration, and invasion.
- Measured ROS production, NADPH oxidase (NOX2, NOX4) and Catalase (CAT) levels.
- Analyzed autophagy markers (Beclin-1, LC3-II/LC3-I, P62) and autophagic flux.
- Investigated the role of ROS scavengers (NAC) and NOX inhibitors (DPI).
- Examined epidermal growth factor receptor (EGFR) activation and its interaction with Beclin-1.
Main Results:
- Blue LED irradiation significantly suppressed OS cell proliferation, migration, and invasion.
- Irradiation increased ROS production via NOX2/NOX4 and decreased CAT levels.
- Autophagy was induced, evidenced by altered protein markers and enhanced flux.
- ROS accumulation and autophagy were crucial for the anti-tumour effects.
- Blue LED irradiation reduced EGFR phosphorylation, leading to Beclin-1 release and autophagy activation.
- Decreased EGFR-Beclin-1 interaction was observed.
Conclusions:
- Blue LED irradiation demonstrates significant anti-tumour effects against human osteosarcoma.
- The mechanism involves ROS generation and the EGFR/Beclin-1-mediated autophagy pathway.
- This therapy represents a potential novel treatment strategy for osteosarcoma.
