title: 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.
abstract: 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.
authors.affiliation: INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4: Inflammation, Cancer, Cellules Souches Cancéreuses, Nice F-06204, France.
authors.forename: Célia
authors.initials: C
authors.lastname: Rosilio
authors.forename: Nadia
authors.initials: N
authors.lastname: Lounnas
authors.forename: Marielle
authors.initials: M
authors.lastname: Nebout
authors.forename: Véronique
authors.initials: V
authors.lastname: Imbert
authors.forename: Thijs
authors.initials: T
authors.lastname: Hagenbeek
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
authors.forename: Vahid
authors.initials: V
authors.lastname: Asnafi
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Pontier-Bres
authors.forename: Julie
authors.initials: J
authors.lastname: Reverso
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.forename: Issam Ben
authors.initials: IB
authors.lastname: Sahra
authors.forename: Fréderic
authors.initials: F
authors.lastname: Bost
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Peyron
mesh_terms: D000483:Alleles; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D016399:Lymphoma, T-Cell / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010629:Phenformin / Q000494:pharmacology*; D012265:Ribonucleotides / Q000494:pharmacology*; D019076:Transgenes
chemical_list: D000970:Antineoplastic Agents; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D008687:Metformin; D010629:Phenformin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C487757:Pten protein, mouse; C031143:AICA ribonucleotide