Exogenous hydrogen sulfide inhibits human melanoma cell development via suppression of the PI3K/AKT/ mTOR pathway

• Published in: Journal of dermatological science Vol. 98; no. 1; pp. 26 - 34
• Main Authors: Xiao, Qing, Ying, Jiayi, Qiao, Zhuhui, Yang, Yiwen, Dai, Xiaoxi, Xu, Zhongyi, Zhang, Chengfeng, Xiang, Leihong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2020
• Subjects: Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; Humans; Hydrogen sulfide; Melanoma; Melanoma - drug therapy; Melanoma - pathology; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT/ mTOR pathway; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Sulfides - pharmacology; Sulfides - therapeutic use; TOR Serine-Threonine Kinases - metabolism; NO; RNA; p-PI3K; GFP; Hydrogen sulfide; NF-κB; PI3K; CSE; CBS; shRNA; FBS; mTOR; PI3K/AKT/ mTOR pathway; ATG7; LC3; Melanoma; H2S; DAPI; IGF-1; Akt; CO; ER; 3-MST; p-Akt; NaHS; TEM; mRFP
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2020.02.004

•Exogenous H2S suppressed cell proliferation, migration and cell cycle progression in melanoma cell lines.•Exogenous H2S induced apoptosis in melanoma cell lines.•Exogenous H2S promotes autophagy in melanoma cell lines.•Suppression of autophagy inhibited melanoma cell development.•Exogenous H2S inhibited melanoma via suppression of PI3K/AKT/mTOR signaling pathway. : 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. : We aimed to explore the effect of exogenous H2S on melanoma cells and its underlying mechanisms. : 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. : 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. : 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.