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Breast Cancer
Published in: Breast Cancer 6/2019

Open Access 01-11-2019 | Breast Cancer | Original Article

Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

Authors: Xia Cheng, Shirui Tan, Feifei Duan, Qingqing Yuan, Qingrong Li, Gang Deng

Published in: Breast Cancer | Issue 6/2019

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Abstract

Background

Icariin is a major component isolated from Epimedium brevicornum Maxim and has been reported to exhibit anti-tumor activity. However, whether icariin could reverse the acquired drug resistance in breast cancer remains largely unclear. Therefore, this study was designed to explore the antitumor effects of icariin and its underlying mechanisms in a tamoxifen-resistant breast cancer cell line MCF-7/TAM.

Methods

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Lactate dehydrogenase (LDH) assay were performed to determine the effects of icariin on cell viability and cell death. Cell cycle progression and apoptosis were detected by flow cytometry analysis. Transmission electron microscopy (TEM) assay was utilized to observe cell autophagy. The downstream protein levels were measured using western blotting.

Results

Here, we observed that icariin treatment not only inhibited the growth of MCF-7 but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Moreover, icariin significantly induced cell cycle G0/G1 phase arrest and apoptosis, as well as suppressed autophagy. At molecular levels, icariin treatment remarkably down-regulated the expression levels of CDK2, CDK4, Cyclin D1, Bcl-2, LC3-1, LC3-II, AGT5, Beclin-1, but upregulated the expression levels of caspase-3, PARP and p62. Most importantly, we found inhibition of autophagy via 3-MA treatment could significantly enhance the effects of icariin on cell viability and apoptosis. Enhanced autophagy via autophagy related 5 (ATG5) overexpression could partially reverse the effects of icariin on cell viability and apoptosis.

Conclusion

These results revealed that icariin might potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen through suppression of autophagy in vitro and provide insight into the therapeutic potential of icariin for the treatment of chemo-resistant breast cancer.
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Metadata
Title
Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM
Authors
Xia Cheng
Shirui Tan
Feifei Duan
Qingqing Yuan
Qingrong Li
Gang Deng
Publication date
01-11-2019
Publisher
Springer Japan
Published in
Breast Cancer / Issue 6/2019
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-019-00980-5

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