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Effects of metformin on breast cancer cell proliferation, the AMPK pathway and the cell cycle

S M Hadad1, D G Hardie, V Appleyard

  • 1Academic Unit of Surgical Oncology, Department of Oncology, The Medical School, University of Sheffield, Sheffield, S10 2RX, UK, s.hadad@sheffield.ac.uk.

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|December 17, 2013
PubMed
Abstract

Insights

Metformin inhibits growth in both ER-positive and ER-negative breast cancer cells by causing G1 cell cycle arrest. This effect is mediated by adenosine monophosphate-activated protein kinase (AMPK) activation and likely involves inhibiting fatty acid synthesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Estrogen receptor (ER)-positive and ER-negative breast cancers exhibit distinct biological behaviors and therapeutic responses.
  • Metformin, a common antidiabetic drug, has demonstrated potential anticancer properties.
  • Understanding metformin's mechanisms in different breast cancer subtypes is crucial for targeted therapy development.

Purpose of the Study:

  • To compare the effects of metformin on ER-positive (MCF-7) and ER-negative (MDA-MB-231) breast cancer cell lines.
  • To elucidate the molecular mechanisms underlying metformin's action, focusing on adenosine monophosphate-activated protein kinase (AMPK) signaling.
  • To investigate metformin's impact on cell proliferation and cell cycle progression.

Main Methods:

  • Cell proliferation was assessed using MTT assays for both cell lines treated with metformin and an AMPK activator (A-769662).
  • Cell cycle analysis was performed using fluorescence-activated cell sorting (FACS).
  • Western blotting was employed to examine the phosphorylation status of AMPK and its downstream targets, including acetyl-CoA carboxylase (ACC).

Main Results:

  • Metformin and A-769662 significantly suppressed cell proliferation in a dose-dependent manner, inducing G1 cell cycle arrest in both ER-positive and ER-negative cells.
  • The anti-proliferative effect was more pronounced in the ER-positive MCF-7 cell line.
  • Metformin treatment led to increased phosphorylation of AMPK and ACC in both cell lines, indicating activation of this pathway.

Conclusions:

  • Metformin exhibits in vitro growth inhibitory effects on both ER-positive and ER-negative breast cancer cells, arresting them in the G1 phase.
  • The observed effects are likely mediated through AMPK activation, potentially by inhibiting fatty acid synthesis via ACC phosphorylation.
  • Metformin represents a potential therapeutic agent for breast cancer, irrespective of ER status, with its efficacy potentially linked to AMPK pathway activation.

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