The combination of metformin and 2-deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells

Autophagy. 2010 Jul;6(5):670-1. doi: 10.1158/0008-5472.CAN-09-2782.

Abstract

Targeting cancer cell metabolism is a new promising strategy to fight cancer. Metformin, a widely used antidiabetic agent, and 2-deoxyglucose (2DG) drastically affect cancer cell metabolism. Recently, we showed that the combination of the two drugs was much more harmful for cancer cells than the treatment with metformin or 2DG alone. At the cellular level, this combination leads to p53- and AMPK-dependent apoptosis. Furthermore, we showed that metformin inhibits 2DG-induced autophagy, decreases beclin 1 expression and triggers a switch from a survival process to cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Antimetabolites / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / genetics
  • Autophagy / drug effects*
  • Beclin-1
  • Deoxyglucose / pharmacology*
  • Drug Synergism
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Membrane Proteins / genetics
  • Metformin / pharmacology*
  • Prostatic Neoplasms / drug therapy*

Substances

  • Antimetabolites
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Hypoglycemic Agents
  • Membrane Proteins
  • Metformin
  • Deoxyglucose
  • AMP-Activated Protein Kinases