title: Inhibition of invasion and epithelial-mesenchymal transition of human breast cancer cells by hydrogen sulfide through decreased phospho-p38 expression.
abstract: Sodium hydrosulfide (NaHS) is an exogenous hydrogen sulfide (H2S)-releasing molecule and has antitumor potential against a wide variety of human cancer types. The effect of exogenous H2S on the invasion of breast cancer and the possible underlying mechanisms remain unknown. The present study aimed to investigate the in vitro effects of H2S on transforming growth factor-β1 (TGF-β1)-induced human breast cancer cells and the associated mechanisms. MCF-7 cells were incubated with TGF-β1 to induce epithelial-mesenchymal transition (EMT) and an MTT assay was performed to detect cell viability. Flow cytometry, using propidium iodide (PI) staining, was used to determine the stages of the cell cycle. Apoptosis was detected with Annexin V-fluorescein isothiocyanate and PI double staining. Western blotting was performed to detect the protein expression of cystathionine γ-lyase (CSE, an endogenous H2S producer), phospho-p38 (a signaling protein associated with apoptosis), and SNAI1 (Snail, associated with the induction of EMT). A Boyden chamber invasion assay was performed to detect tumor invasion. The results demonstrated that when NaHS was administered to TGF-β1-treated MCF-7 cells, the cells exhibited decreased proliferation, G0/G1 phase cell cycle arrest and increased apoptosis. NaHS treatment following TGF-β1 administration also resulted in decreased cell invasion and decreased EMT, which was indicated by decreased Snail protein expression. In addition, incubation with NaHS increased endogenous CSE protein expression and decreased p38 mitogen-activated protein kinase phosphorylation in MCF-7 cells stimulated by TGF-β1. Furthermore, the inhibition of endogenous CSE by DL-propargylglycine increased EMT in the MCF-7 cells treated with NaHS and TGF-β1. In conclusion, the present study provides insights into a novel anticancer effect of H2S on breast cancer cells through activation of the CSE/H2S pathway and decreased expression of phospho-p38.
authors.affiliation: Department of Scientific Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Lv
authors.affiliation: Department of Oncology, Lianyungang First People's Hospital, Lianyungang, Jiangsu 222002, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Radiotherapy, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Ji
authors.affiliation: Department of Oncology, Lianyungang First People's Hospital, Lianyungang, Jiangsu 222002, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhuang
authors.affiliation: Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Jin-Hai
authors.initials: JH
authors.lastname: Tang
mesh_terms: D000480:Alkynes / Q000633:toxicity; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives / Q000633:toxicity; D006801:Humans; D006862:Hydrogen Sulfide / Q000633:toxicity*; D061986:MCF-7 Cells; D010766:Phosphorylation / Q000187:drug effects; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000480:Alkynes; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C009055:propargylglycine; D048051:p38 Mitogen-Activated Protein Kinases; D003542:Cystathionine gamma-Lyase; D005998:Glycine; D006862:Hydrogen Sulfide