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.

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.

Metformin and cancer therapy.

PURPOSE OF REVIEW: To focus on the potential role of metformin, a widely used antidiabetic drug, in cancer treatment. RECENT FINDINGS: Epidemiological, preclinical and cellular studies have shown in the last 6 years that metformin exerts antitumoral properties. Here, we review the very last findings concerning metformin action in cancer. The results of the first clinical trials as well as the combined action of metformin and chemotherapeutics agents in vitro and in vivo will be discussed. Recent studies show that metformin could also regulate inflammation and, therefore, may play a role in tumor microenvironment. Finally, we will present the latest publications concerning the molecular mechanisms implicated in metformin action, especially the AMP-activated kinase-independent pathways. SUMMARY: The numerous in-vitro and in-vivo studies warrant the ongoing clinical trials, which should definitively help us to determine if metformin could be used in cancer therapy.