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

Gao,Zhen‑Yuan; Liu,Zhe; Bi,Ming‑Hong; Zhang,Jing‑Jing; Han,Zheng‑Quan; Han,Xiao; Wang,Hong‑Ya; Sun,Guo‑Ping; Liu,Hao

doi:10.3892/etm.2016.3143

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
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Affiliations: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032. P.R. China, Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui 233030, P.R. China, Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233022, P.R. China
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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