Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro
| Autor: | Zhen‑Yuan Gao, Ming‑Hong Bi, Zhe Liu, Zheng‑Quan Han, Xiao Han, Hao Liu, Guo‑Ping Sun, Hong‑Ya Wang, Jing-Jing Zhang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty mediated pathway endocrine system diseases Cell Biology 03 medical and health sciences breast cancer 0302 clinical medicine Immunology and Microbiology (miscellaneous) Internal medicine medicine Viability assay Oncogene apoptosis Cancer Articles General Medicine Cell cycle medicine.disease Metformin mitochondria 030104 developmental biology Endocrinology medicine.anatomical_structure Apoptosis 030220 oncology & carcinogenesis Cancer cell Cancer research metformin medicine.drug |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-1015 1792-0981 |
| DOI: | 10.3892/etm.2016.3143 |
| Popis: | Breast cancer is the most commonly occurring cancer and second leading cause of mortality in women. Metformin is a widely prescribed anti-hyperglycemic drug, which is emerging as a potential cancer preventative and treatment agent. However, the mechanisms underlying the suppressive effects of metformin on cancer cell growth and the induction of cancer cell apoptosis are not fully elucidated. The present study aimed to identify the pathways regulated by metformin in two breast cancer cell lines, MDA-MB-231 and MDA-MB-435. Cells were treated with various concentrations of metformin and then evaluated with respect to viability, proliferation, adenosine triphosphate (ATP) and reactive oxygen species (ROS) levels, mitochondrial membrane potential (∆ψm), and the expression of anti- and pro-apoptotic proteins. Metformin caused apoptosis in a concentration- and time-dependent manner, and decreased cell viability and ATP production. Furthermore, metformin induced the generation of ROS and decreased the ∆ψm. Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells. These results demonstrate that the apoptotic and cytotoxic effects of metformin on breast cancer cells are mediated by the intrinsic mitochondria-mediated apoptosis pathway. |
| Databáze: | OpenAIRE |
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