Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/116781
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Type: Journal article
Title: Inhibiting autophagy increases epirubicin's cytotoxicity in breast cancer cells
Author: Guo, W.
Wang, Y.
Wang, Z.
Wang, Y.-.P.
Zheng, H.
Citation: Cancer Science, 2016; 107(11):1610-1621
Publisher: Wiley
Issue Date: 2016
ISSN: 1347-9032
1349-7006
Statement of
Responsibility: 
Wei Guo, Yu Wang, Zhu Wang, Yan-Ping Wang and Hong Zheng
Abstract: Chemotherapy, radiotherapy, and endocrinotherapy are documented to induce autophagy among breast cancer cells, but the role of autophagy in this disease has been attributed as cytoprotective as well as tumor-suppressing. Thus we studied MDA-MB-231 and SK-BR-3 breast cancer cell lines treated with epirubicin (EPI) to assess autophagy and apoptosis. We found out that EPI induced apoptosis and autophagy in both cell lines. The lysosomal inhibitor bafilomycin A1 inhibited cellular autophagy and enhanced EPI-triggered apoptosis, perhaps due to inhibition of autolysosome formation, which then inhibited autophagic effects of engulfing and clearing damaged mitochondria. This inhibition increased mitochondrial cytochrome C release which augmented epirubicin-induced caspase-dependent apoptosis and cytotoxicity. In addition, the lysosomal neutralizing agent ammonia chloride (AC), and Atg7 knockdown by siRNA, could inhibit epirubicin-triggered autophagy, enhance cytotoxicity, and increase caspase-9- and caspase-3-dependent apoptosis. Thus, autophagy plays a prosurvival role in EPI-treated MDA-MB-231 and SK-BR-3 cells, and autophagy inhibition can potentially reverse this effect and increase the cytotoxicity of EPI.
Keywords: Autophagy; bafilomycin A1; breast cancer; cytotoxicity; epirubicin
Rights: © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is noncommercial and no modifications or adaptations are made.
RMID: 0030077204
DOI: 10.1111/cas.13059
Appears in Collections:Medicine publications

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