Fluoxetine induces autophagic cell death via eEF2K-AMPK-mTOR-ULK complex axis in triple negative breast cancer

Cell Proliferation
Dejuan SunLiang Ouyang

Abstract

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. 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. 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. These results demonstrate that Fluoxetine ...Continue Reading

References

Nov 9, 2007·Apoptosis : an International Journal on Programmed Cell Death·Andrew Thorburn
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Jun 24, 2009·Molecular Oncology·Shai White-GilbertsonChristina Voelkel-Johnson
Nov 3, 2010·Cancer Letters·Jun-jie LiuJin-ku Bao
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Oct 26, 2011·Molecular and Cellular Biology·Sebastian AlersBjörn Stork
Oct 16, 2012·Biological Psychiatry·Lisa M MonteggiaEge T Kavalali
May 2, 2013·Therapeutic Advances in Medical Oncology·John Stagg, Bertrand Allard
Jun 19, 2013·Biochimica Et Biophysica Acta·Vassiliki NikoletopoulouNektarios Tavernarakis
Jun 25, 2013·Cancer Letters·Zheng ShiJin-ku Bao
Jul 16, 2014·Apoptosis : an International Journal on Programmed Cell Death·L L FuB Liu
Sep 6, 2015·Archives of Gynecology and Obstetrics·Pankaj Kumar, Rupali Aggarwal
Nov 6, 2015·Trends in Pharmacological Sciences·Murugan KalimuthoKum Kum Khanna
May 5, 2016·Nature·Roberto Malinow
Jul 10, 2016·Toxicology Letters·Marcos Roberto de Oliveira
Jul 20, 2016·Pharmacology Research & Perspectives·Vitor CaiaffoJoaquim Evêncio Neto
Jul 28, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Anita K BakraniaSnehal S Patel
Jan 16, 2017·Molecular and Cellular Endocrinology·Nikolas Balanis, Cathleen R Carlin

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Citations

Feb 8, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Zuhal HamurcuBulent Ozpolat
May 8, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Didem Karakas, Bulent Ozpolat
Sep 8, 2020·Journal of Zhejiang University. Science. B·Nan WenZheng-Gui Du
Jun 4, 2019·Frontiers in Psychiatry·Nils C Gassen, Theo Rein
May 15, 2020·Journal of Bioenergetics and Biomembranes·Seyed Jalal HosseinimehrHossein Asgarian-Omran
Oct 30, 2020·International Journal of Molecular Sciences·Polina V ShnaiderVictoria O Shender
Aug 6, 2021·Pathology, Research and Practice·Mingxia JiangChengxin Song
Nov 4, 2021·Drug Discovery Today·Yihui SongBin Yu
Jun 21, 2020·Anti-cancer Agents in Medicinal Chemistry·Milad AshrafizadehAmirhossein Sahebkar

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