title: Autophagy induced by a sulphamoylated estrone analogue contributes to its cytotoxic effect on breast cancer cells.
abstract: BACKGROUND
  Autophagy can either be protective and confer survival to stressed cells, or it can contribute to cell death. The antimitotic drug 2-ethyl-3-O-sulpamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) is an in silico-designed 17-β-estradiol analogue that induces both autophagy and apoptosis in cancer cells. The aim of the study was to determine the role of autophagy in ESE-15-ol-exposed human adenocarcinoma breast cancer cells; knowledge that will contribute to future clinical applications of this novel antimitotic compound. By inhibiting autophagy and determining the cytotoxic effects of ESE-15-ol-exposure, deductions could be made as to whether the process may confer resistance to the drug, or alternatively, contribute to the cell death process.
  
  
  RESULTS
  Spectophometrical analysis via crystal violet staining was used to perform cytotoxicity studies. Morphology studies were done using microscopic techniques namely polarization-optical transmitted light differential interference light microscopy, fluorescent microscopy using monodansylcadaverine staining and transmission electron microscopy. Flow cytometry was used to quantify the autophagy inhibition and assess cell viability. Results obtained indicated that 3-methyladenine inhibited autophagy and increased cell survival in both MCF-7 and MDA-MB-231 cell lines.
  
  
  CONCLUSIONS
  This in vitro study inferred that autophagy inhibition with 3-methyladenine does not confer increased effectiveness of ESE-15-ol in inducing cell death. Thus it may be concluded that the autophagic process induced by ESE-15-ol exposure in MCF-7 and MDA-MB-231 cells plays a more significant role in cell death than conferring survival.
authors.affiliation: Department of Physiology, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Arcadia, Pretoria, 0007 Gauteng South Africa.
authors.forename: Marcel
authors.initials: M
authors.lastname: Verwey
authors.affiliation: Department of Physiology, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Arcadia, Pretoria, 0007 Gauteng South Africa.
authors.forename: Elsie M
authors.initials: EM
authors.lastname: Nolte
authors.affiliation: Department of Physiology, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Arcadia, Pretoria, 0007 Gauteng South Africa.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Joubert
authors.affiliation: Department of Physiology, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Arcadia, Pretoria, 0007 Gauteng South Africa.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Theron
keywords: 3-Methyladenine; Apoptosis; Autophagy; Breast cancer; Cell survival; ESE-15-ol