Autophagy induced by a sulphamoylated estrone analogue contributes to its cytotoxic effect on breast cancer cells

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Authors

Verwey, M.
Nolte, Elsie Magdalena
Joubert, Annie M.
Theron, Anne Elisabeth

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BioMed Central

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. METHODS AND 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 MDAMB- 231 cell lines. CONCLUSION : 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.

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Breast cancer, Autophagy, Apoptosis, Cell survival, ESE-15-ol, 3-Methyladenine

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Citation

Verwey, M, Nolte, EM, Joubert, AM & Theron, AE 2016, 'Autophagy induced by a sulphamoylated estrone analogue contributes to its cytotoxic effect on breast cancer cells', Cancer Cell International, vol. 16, art. no. 91, pp. 1-17.