Open Access

Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro

  • Authors:
    • Zhen‑Yuan Gao
    • Zhe Liu
    • Ming‑Hong Bi
    • Jing‑Jing Zhang
    • Zheng‑Quan Han
    • Xiao Han
    • Hong‑Ya Wang
    • Guo‑Ping Sun
    • Hao Liu
  • View Affiliations

  • Published online on: March 10, 2016     https://doi.org/10.3892/etm.2016.3143
  • Pages: 1700-1706
  • Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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May 2016
Volume 11 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
APA
Gao, Z., Liu, Z., Bi, M., Zhang, J., Han, Z., Han, X. ... Liu, H. (2016). Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro. Experimental and Therapeutic Medicine, 11, 1700-1706. https://doi.org/10.3892/etm.2016.3143
MLA
Gao, Z., Liu, Z., Bi, M., Zhang, J., Han, Z., Han, X., Wang, H., Sun, G., Liu, H."Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro". Experimental and Therapeutic Medicine 11.5 (2016): 1700-1706.
Chicago
Gao, Z., Liu, Z., Bi, M., Zhang, J., Han, Z., Han, X., Wang, H., Sun, G., Liu, H."Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro". Experimental and Therapeutic Medicine 11, no. 5 (2016): 1700-1706. https://doi.org/10.3892/etm.2016.3143