The Antiproliferative Potential and Mechanism of Action of Metformin in MCF-7 Cells

Abstract

Aim: The current study aimed to investigate the potential antiproliferative activity of metformin, the effective concentration range, and the mechanism of action. Materials & methods: Human breast cancer cells, MCF-7 were treated with a serial dilution of metformin (10–150 μM) for 24 and 48 h. Potential antiproliferative activity of metformin and its ability in inducing cellular apoptosis and autophagy were also investigated. Results: Metformin inhibited MCF-7 proliferation in a concentration and time dependent manner, with 80 μM as the most effective concentration. Compared with nontreated cells, metformin induced significant levels of autophagy and apoptosis, which were confirmed by the reduction of mTOR and BCL-2 protein expression. Conclusion: The study confirms the antiproliferative activity of metformin, which may likely occur through AMPK signaling pathway.

Plain Language Summary

The antidiabetic drug, metformin is tested in this work for its possible ability to inhibit the growth of breast cancer cells. Using different concentrations of the drug over different time points, the results showed that the drug was able to inhibit cancer growth through different mechanisms. The results also showed that the drug inhibits cancer growth by stimulating program cell death (apoptosis), as well as autophagy, where the cell breaks old and abnormal cellular substances.

Keywords:

• antiproliferative
• apoptosis
• autophagy
• breast cancer
• metformin

Author contributions

Z Bekezhankyzy: conducted most of the research and wrote the first draft; S Nurzhan and N Berdigaliyev: conducted western blots and data analysis; S Sergazy and T Maulenkul: drug testing and data analysis; M Aljofan: provided funding, research supervision and manuscript writing. All authors have read and agreed to the manuscript.

Acknowledgments

The authors thank the Nazarbayev University School of Medicine for providing some of the chemicals and materials used in this work.

Financial & competing interests disclosure

This research was partially funded by the NUSOM-Social Policy Grant awarded to M Aljofan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.