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Exogenous hydrogen sulfide inhibits human melanoma cell development via suppression of the PI3K/AKT/ mTOR pathway
Qing Xiao1, Jiayi Ying1, Zhuhui Qiao1
1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, PR China.
Background:
Melanoma is one of the most aggressive, therapy-resistant skin cancers in the world. Hydrogen sulfide (H2S), a newly discovered gasotransmitter, plays a crucial role in the progression and development of many types of cancers. However, the effect of H2S on human skin melanoma remains to be elucidated.
Objective:
We aimed to explore the effect of exogenous H2S on melanoma cells and its underlying mechanisms.
Methods:
In this study, human skin melanoma cell lines, including A375 and SK-MEL-28, were treated with a donor of H2S (NaHS). CCK-8, scratch assay, flow cytometric analysis, western blotting and transmission electron microscopy (TEM) were performed to explore the effects of H2S on cell behaviors.
Results:
Treatment with NaHS inhibited cell proliferation, migration and division, while it could induce cell apoptosis and autophagy in melanoma cell lines. Moreover, NaHS significantly decreased the expression of p-PI3K, p-Akt and mTOR proteins. Furthermore, insulin-like growth factor-1 (IGF-1), the activator of PI3K/AKT/mTOR pathway, could reverse the cell behaviors caused by NaHS.
Conclusion:
Our results demonstrated that exogenous hydrogen sulfide could inhibit human melanoma cell development via suppression of the PI3K/AKT/mTOR pathway. Hydrogen sulfide might serve as a potential therapeutic option for melanoma.
Insights
Hydrogen sulfide (H2S) inhibits melanoma cell growth, migration, and division. This gasotransmitter may offer a new therapeutic strategy for melanoma by targeting the PI3K/AKT/mTOR pathway.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Melanoma is an aggressive skin cancer with limited therapeutic options.
- Hydrogen sulfide (H2S), a gasotransmitter, influences cancer progression.
- The role of H2S in human melanoma is not well understood.
Purpose of the Study:
- To investigate the effects of exogenous H2S on human melanoma cells.
- To elucidate the molecular mechanisms underlying H2S action in melanoma.
Main Methods:
- Human melanoma cell lines (A375, SK-MEL-28) were treated with a hydrogen sulfide donor (NaHS).
- Cell proliferation, migration, and apoptosis were assessed using CCK-8, scratch assays, and flow cytometry.
- Western blotting and transmission electron microscopy (TEM) were used to analyze protein expression and cellular changes.
Main Results:
- NaHS treatment inhibited melanoma cell proliferation, migration, and division.
- H2S induced apoptosis and autophagy in melanoma cells.
- NaHS decreased the expression of p-PI3K, p-Akt, and mTOR; IGF-1 reversed these effects.
Conclusions:
- Exogenous hydrogen sulfide inhibits human melanoma cell development by suppressing the PI3K/AKT/mTOR pathway.
- Hydrogen sulfide presents a potential therapeutic avenue for melanoma treatment.
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