title: Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cellsin vitro.
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.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032. P.R. China.
authors.forename: Zhen-Yuan
authors.initials: ZY
authors.lastname: Gao
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui 233030, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233022, P.R. China.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Bi
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233022, P.R. China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233022, P.R. China.
authors.forename: Zheng-Quan
authors.initials: ZQ
authors.lastname: Han
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233022, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233022, P.R. China.
authors.forename: Hong-Ya
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032. P.R. China.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Sun
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui 233030, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
keywords: apoptosis; breast cancer; mediated pathway; metformin; mitochondria