Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Metformin promotes apoptosis of A549 cells via regulation of p-AMPK protein expression, bax/bcl-2 ratio and ROS levels

Ziying Yu¹, Fengtao Liu², Xiaoli Zhang³

¹Department of Emergency, The First Affiliated Hospital of University of South China; ²Center of Functional Laboratory, Hengyang Medical College, The University of South China; ³Department of Pathology, The First Affiliated Hospital of University of South China, Hengyang 421001, Hunan Province, China.

For correspondence:- Xiaoli Zhang Email: zxldyc2020@163.com

Accepted: 16 August 2021 Published: 30 September 2021

Citation: Yu Z, Liu F, Zhang X. Metformin promotes apoptosis of A549 cells via regulation of p-AMPK protein expression, bax/bcl-2 ratio and ROS levels. Trop J Pharm Res 2021; 20(9):1827-1832 doi: 10.4314/tjpr.v20i9.7

© 2021 The authors.
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Abstract

Purpose: To investigate the influence of metformin on apoptosis of pulmonary carcinoma cells (A549), and the associated mode of action.

Methods: Pulmonary carcinoma cells in logarithmic growth phase were treated with graded concentrations of metformin, and the anti-proliferative and apoptotic effects of the drug were measured using MTT assay and flow cytometry, respectively. The levels of reactive oxygen species (ROS) in A549 cell suspension were determined with 2, 7- dihydrodichlorofluorescein diacetate (DCFH-DA) assay. The expression levels of phosphorylated AMP-activated protein kinase (p-AMPK), mammalian target of rapamycin (mTOR), and bax/bcl-2 ratio were measured using Western blotting and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR).

Results: Metformin significantly promoted A549 cell apoptosis, but suppressed its proliferative potential in a dose- and time-based fashion. The levels of ROS, superoxide anion and MDA in A549 cells were significantly and dose-dependently increased by metformin (p < 0.05). Moreover, metformin markedly upregulated the mRNA and protein expressions of p-AMPK as well as bax/bcl-2 ratio, but had no impact on the expression level of mTOR (p < 0.05).

Conclusion: Metformin promotes apoptosis in A549 cells via regulation of p-AMPK protein expression, bax/bcl-2 ratio, and ROS levels, and hence may play a role in lung cancer therapy.

Keywords: Apoptosis, Lung cancer, Metformin, Proliferation, Reactive oxygen species