# Metformin‐Mediated Glycaemic Regulation as a Potential Strategy for Breast Cancer Prevention

## TL;DR

Metformin, a diabetes drug, may help prevent breast cancer by activating anti-cancer pathways and altering tumor environments.

## Contribution

This paper reviews in vitro mechanisms by which metformin exerts anti-cancer effects on breast cancer cells.

## Key findings

- Metformin activates AMPK to induce anti-proliferation and cell cycle arrest in breast cancer cells.
- AMPK-independent effects include metastasis inhibition, apoptosis, and synergism with chemotherapy.
- Metformin alters the tumor microenvironment and induces ferroptosis in breast cancer cells.

## Abstract

Metformin, the common anti‐hyperglycemic agent, is emerging with pharmacological significance as an effective anti‐cancer modulator. Its efficacy as an anti‐cancer modulator is reported in pre‐clinical and clinical studies. Therefore, an attempt was made to identify the possible in vitro anti‐cancer molecular mechanisms studied on breast cancer (BC) cell lines.

An advanced literature search was conducted in the PubMed database using search terms “Metformin, Cell culture, Breast neoplasms.” Different anti‐cancer molecular mechanisms induced by metformin (MET) identified in cell culture studies are presented in this paper.

It was identified that MET induces molecular pathways that exert anti‐cancer effects when treated on BC cells. Inhibition of oxidative phosphorylation, adenosine monophosphate‐activated protein kinase mediated anticancer effects, anti‐proliferation and inhibition of cell migration, alteration of tumor micro‐environment, synergetic effects with conventional chemotherapies and other potential molecules, induced apoptosis and ferroptosis were mainly identified as MET‐induced pathways that affect BC cells.

Metformin induces diverse anti‐cancer biochemical pathways through which it exhibits a potential to be used as an anti‐cancer therapeutic in BC.

Metformin (MET), a common antihyperglycemic drug, shows promising anti‐cancer effects in breast cancer (BC). It activates adenosine monophosphate‐activated protein kinase (AMPK), regulating cellular energy and inducing cell cycle arrest, anti‐proliferation, and microenvironment alterations. AMPK‐independent mechanisms include metastasis inhibition, drug synergism, ferroptosis, and apoptosis, highlighting MET's potential for novel BC therapies.