The metabolic perturbators metformin, phenformin and AICAR interfere with the growth and survival of murine PTEN-deficient T cell lymphomas and human T-ALL/T-LL cancer cells

Célia Rosilio, Nadia Lounnas, Marielle Nebout, Véronique Imbert, Thijs Hagenbeek, Hergen Spits, Vahid Asnafi, Rodolphe Pontier-Bres, Julie Reverso, Jean François Michiels, Issam Ben Sahra, Fréderic Bost, Jean François Peyron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The antidiabetics metformin/phenformin and the AMPK activator AICAR exert anti-leukemic effects. The compounds inhibited tumor metabolism and proliferation and induced apoptosis. Effects were associated with AMPK activation and inhibition of constitutive mTOR. The metabolic perturbators potentiated the action of classical anti-leukemic drugs. We show here that the antidiabetic agents metformin and phenformin and the AMPK activator AICAR exert strong anti-tumoural effects on tPTEN-/- lymphoma cells and on human T-ALL cell lines and primary samples. The compounds act by inhibiting tumour metabolism and proliferation and by inducing apoptosis in parallel with an activation of AMPK and an inhibition of constitutive mTOR. In tPTEN-/- cells, the drugs potentiated the anti-leukaemic effects of dexamethasone, and metformin and phenformin synergised with 2-deoxyglucose (2DG) to impair tumour cell survival. In vivo, metformin and AICAR strongly decreased the growth of luciferase-expressing tPTEN-/- cells xenografted in Nude mice, demonstrating that metabolism targeting could be a potent adjuvant strategy for lymphoma/leukaemia treatment.

Original languageEnglish (US)
Pages (from-to)114-126
Number of pages13
JournalCancer Letters
Volume336
Issue number1
DOIs
StatePublished - Aug 9 2013

Keywords

  • AICAR
  • AMPK
  • Leukaemia
  • MTOR
  • Metformin
  • PTEN

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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