Open AccessInhibiting autophagy increases epirubicin's cytotoxicity in breast cancer cells
Author(s) -
Guo Wei,
Wang Yu,
Wang Zhu,
Wang YanPing,
Zheng Hong
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13059
Subject(s) - autophagy , cytotoxicity , apoptosis , epirubicin , cancer research , programmed cell death , lysosome , cancer cell , chemistry , bafilomycin , microbiology and biotechnology , cell culture , biology , cancer , breast cancer , biochemistry , in vitro , genetics , enzyme
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 si RNA , 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 .