Cantharidin Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing Autophagy and Inducing Apoptosis in Vitro and in Vivo
| Autor: | Wen Feng, Ke Xu, Zhi-Hua Xia, Yi Mei, Dian-xu Feng, Han Cai, Yi-ming Jiang, Ya-feng Chen, Hong-chang Li, Fan Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Physiology Blister beetle Mice Nude Triple Negative Breast Neoplasms Apoptosis lcsh:Physiology Flow cytometry lcsh:Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice Triple-negative breast cancer Cell Line Tumor medicine In Situ Nick-End Labeling Autophagy Animals Humans lcsh:QD415-436 Enzyme Inhibitors Cantharidin biology medicine.diagnostic_test lcsh:QP1-981 Cell growth biology.organism_classification Xenograft Model Antitumor Assays 030104 developmental biology chemistry Cell culture Cancer research Beclin-1 Mylabris phalerata |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 43, Iss 5, Pp 1829-1840 (2017) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: Cantharidin, a type of terpenoid secreted by the blister beetle Mylabris phalerata (Pallas), has attracted great attention in cancer therapy because of its potential anti-cancer activities. Here, we report the effects on apoptosis and autophagy in human triple-negative breast cancer (TNBC) cell lines after treatment with cantharidin and attempt to elucidate the underlying mechanisms. Methods: MDA-MB-231 and MDA-MB-468 cells were treated with cantharidin and cell proliferation was examined using CCK-8 and clone formation assays. The expression of apoptosis- and autophagy-associated proteins was detected by western blotting. Cells were infected with lentivirus carrying the Beclin-1 gene, and MDA-MB-231-beclin1 (MB231-Bec) and MDA-MB-468-beclin-1(MB468-Bec) cells stably expressing Beclin-1 were established. Autophagic vacuoles in cells were observed with LC3 staining using fluorescence microscopy, and apoptotic cells were detected via flow cytometry. Tumor growth was assessed by subcutaneous inoculation of TNBC cells into BALB/c nude mice. Results: Cantharidin inhibited the proliferation of MDA-MB-231 and MDA-MB-468 cells, and induced cell apoptosis. Cantharidin additionally inhibited the conversion of LC3 I to LC3 II and autophagosome formation by suppressing the expression of Beclin-1. Furthermore, overexpression of Beclin-1 in TNBC cells attenuated the cytotoxicity of cantharidin. In vivo, cantharidin inhibited the growth of MDA-MB-231 and MDA-MB-468 xenografts in nude mice by suppressing autophagy and inducing apoptosis, and Beclin-1 overexpression in TNBC cells reduced the efficacy of cantharidin. Conclusions: Cantharidin inhibits autophagy by suppressing Beclin-1 expression and inducing apoptosis of TNBC cells in vitro and in vivo, thereby representing a potential strategy for the treatment of TNBC. |
| Databáze: | OpenAIRE |
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