Abstract
BackgroundIcariin 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.Methods3-(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.ResultsHere, 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.ConclusionThese 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.
Highlights
Breast cancer, the most common diagnosed cancer in women in the worldwide, is a heterogenous disease with multiple histological subtypes [1]
We aimed to investigate the biological function of icariin in TAM resistance in breast cancer cells by presenting some evidences regarding the activity of icariin on viability, Lactate dehydrogenase (LDH) cytotoxicity, cell cycle progression, apoptosis, and autophagy of MCF-7/TAM cells
To investigate the cytotoxic effect of icariin in breast cancer cells, two TAM-sensitive breast cancer cell lines and the corresponding TMA-resistant cell lines were treated with icariin at increasing concentrations for 24 h
Summary
The most common diagnosed cancer in women in the worldwide, is a heterogenous disease with multiple histological subtypes [1]. Acquired resistance to tamoxifen limits its therapeutic effectiveness and results in rapid disease progression in breast cancer patients [6]. 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. Results Here, we observed that icariin treatment inhibited the growth of MCF-7 and has a potential function to overcome tamoxifen resistance in MCF-7/TAM. We found inhibition of autophagy via 3-MA treatment could significantly enhance 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
