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Metformin prevents cell tumorigenesis through autophagy-related cell death

Mauro De Santi1, Giulia Baldelli2, Aurora Diotallevi3

  • 1Department of Biomolecular Sciences, Hygiene Unit, University of Urbino Carlo Bo, Urbino (PU), Italy. mauro.desanti@uniurb.it.

Scientific Reports
|January 13, 2019
PubMed

Insights

Metformin promotes cell death via autophagy, a cellular process that eliminates damaged components. This suggests autophagy-related cell death can eliminate precancerous cells, offering a novel cancer prevention strategy.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Autophagy

Background:

  • Autophagy maintains cellular homeostasis by degrading intracellular components.
  • Metformin, an autophagy inducer, shows chemopreventive properties.
  • The role of autophagy in cancer prevention requires further investigation.

Purpose of the Study:

  • To investigate the autophagy-related effects of metformin on cancer initiation and progression.
  • To analyze tumorigenesis induction in autophagy-deficient cells and its link to ER stress.

Main Methods:

  • Utilized preneoplastic JB6 Cl 41-5a and NIH/3T3 cells.
  • Administered tumor promoter (phorbol) and H2O2 for stress induction.
  • Employed wortmannin and ATG7 silencing to inhibit autophagy.
  • Assessed tumorigenesis and unfolded protein response (UPR) markers.

Main Results:

  • Metformin induced significant cell death in stressed preneoplastic and NIH/3T3 cells.
  • Autophagy inhibition reduced metformin's cytotoxic effect, indicating autophagy-dependent cell death.
  • ATG7-silenced cells showed induced tumorigenesis and UPR marker upregulation under stress.

Conclusions:

  • Autophagic cell death is a mechanism for eliminating damaged cells.
  • Metformin's cytotoxic effect is mediated by autophagy.
  • Autophagy-related cell death presents a promising strategy for eliminating potential tumorigenic cells.

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