{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":44,"searchCount":0},"additional":{"submitter":["Sun D"],"funding":["National Key R&amp;D Program of China","National Natural Science Foundation of China"],"pagination":["e12402"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6528897"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["51(2)"],"pubmed_abstract":["<h4>Objectives</h4>Triple negative breast cancer (TNBC) is a complex and intrinsically aggressive tumour with poor prognosis, and the discovery of targeted small-molecule drugs for TNBC treatment still remains in its infancy. In this study, we aimed to discover a small-molecule agent for TNBC treatment and illuminate its potential mechanisms.<h4>Materials and methods</h4>Cell viability was detected by using methylthiazoltetrazolium (MTT) assay. Electron microscopy, GFP-LC3 transfection, monodansylcadaverine staining and apoptosis assay were performed to determine Fluoxetine-induced autophagy and apoptosis. Western blotting and siRNA transfection were carried out to investigate the mechanisms of Fluoxetine-induced autophagy. iTRAQ-based proteomics analysis was used to explore the underlying mechanisms.<h4>Results</h4>We have demonstrated that Fluoxetine had remarkable anti-proliferative activities and induced autophagic cell death in MDA-MB-231 and MDA-MB-436 cells. The mechanism for Fluoxetine-induced autophagic cell death was associated with inhibition of eEF2K and activation of AMPK-mTOR-ULK complex axis. Further iTRAQ-based proteomics and network analyses revealed that Fluoxetine-induced mechanism was involved in BIRC6, BNIP1, SNAP29 and Bif-1.<h4>Conclusions</h4>These results demonstrate that Fluoxetine induces apoptosis and autophagic cell death in TNBC, which will hold a promise for the future TNBC therapy."],"journal":["Cell proliferation"],"pubmed_title":["Fluoxetine induces autophagic cell death via eEF2K-AMPK-mTOR-ULK complex axis in triple negative breast cancer."],"pmcid":["PMC6528897"],"funding_grant_id":["2017YFC0909301","81602984","81603275"],"pubmed_authors":["Jiang Y","Zhu L","Chen L","Sun D","Ouyang L","Zhao Y","Yu Y"],"view_count":["44"],"additional_accession":[]},"is_claimable":false,"name":"Fluoxetine induces autophagic cell death via eEF2K-AMPK-mTOR-ULK complex axis in triple negative breast cancer.","description":"<h4>Objectives</h4>Triple negative breast cancer (TNBC) is a complex and intrinsically aggressive tumour with poor prognosis, and the discovery of targeted small-molecule drugs for TNBC treatment still remains in its infancy. In this study, we aimed to discover a small-molecule agent for TNBC treatment and illuminate its potential mechanisms.<h4>Materials and methods</h4>Cell viability was detected by using methylthiazoltetrazolium (MTT) assay. Electron microscopy, GFP-LC3 transfection, monodansylcadaverine staining and apoptosis assay were performed to determine Fluoxetine-induced autophagy and apoptosis. Western blotting and siRNA transfection were carried out to investigate the mechanisms of Fluoxetine-induced autophagy. iTRAQ-based proteomics analysis was used to explore the underlying mechanisms.<h4>Results</h4>We have demonstrated that Fluoxetine had remarkable anti-proliferative activities and induced autophagic cell death in MDA-MB-231 and MDA-MB-436 cells. The mechanism for Fluoxetine-induced autophagic cell death was associated with inhibition of eEF2K and activation of AMPK-mTOR-ULK complex axis. Further iTRAQ-based proteomics and network analyses revealed that Fluoxetine-induced mechanism was involved in BIRC6, BNIP1, SNAP29 and Bif-1.<h4>Conclusions</h4>These results demonstrate that Fluoxetine induces apoptosis and autophagic cell death in TNBC, which will hold a promise for the future TNBC therapy.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Apr","modification":"2024-11-20T23:54:43.596Z","creation":"2020-05-22T12:21:52Z"},"accession":"S-EPMC6528897","cross_references":{"pubmed":["29094413"],"doi":["10.1111/cpr.12402"]}}