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Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside?

Cecilia Marini1,2, Vanessa Cossu3, Matteo Bauckneht2,3

  • 1CNR Institute of Molecular Bioimaging and Physiology (IBFM), 20054 Milan, Italy.

Biomolecules
|August 27, 2021
PubMed

Insights

Metformin, a diabetes drug, may fight cancer by disrupting tumor energy and growth. It also uniquely inhibits glucose uptake by affecting hexose-6P-dehydrogenase (H6PD) and endoplasmic reticulum metabolism.

Area of Science:

  • Oncology
  • Metabolism
  • Pharmacology

Background:

  • Metformin, a common type 2 diabetes medication, has shown potential anticancer effects in various studies.
  • Its anti-cancer properties are partly attributed to inhibiting cancer cell energy production via AMP-activated protein kinase (AMPK) and blocking oxidative phosphorylation (OXPHOS).

Purpose of the Study:

  • To explore the anticancer mechanisms of metformin beyond OXPHOS inhibition.
  • To investigate metformin's effect on glucose uptake and its potential role in cancer metabolism.

Main Methods:

  • Review of in vitro and in vivo experimental studies on metformin's effects.
  • Analysis of metformin's impact on 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG) uptake.
  • Examination of metformin's interaction with hexose-6P-dehydrogenase (H6PD) and the pentose-phosphate pathway (PPP) within the endoplasmic reticulum (ER).

Main Results:

  • Metformin selectively inhibits FDG uptake by impairing H6PD catalytic function.
  • This inhibition affects the pentose-phosphate pathway (PPP) in the endoplasmic reticulum (ER), impacting NADPH production.
  • Metformin's actions on ER metabolism and H6PD may influence cancer cell proliferation and antioxidant responses.

Conclusions:

  • Metformin exhibits anticancer potential through novel mechanisms involving H6PD and ER metabolism, distinct from its effects on OXPHOS.
  • Targeting ER metabolism could be a new therapeutic strategy for solid cancers.
  • H6PD activation may be a biomarker for cancer aggressiveness detectable by PET/CT scans.
Keywords:
FDG PET/CT imagingcancer therapyendoplasmic reticulumglucose consumptionmetformintumor metabolism

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