title: Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models.
abstract: Discovery of new drugs for cancer treatment is an expensive and time-consuming process and the percentage of drugs reaching the clinic remains quite low.Drug repositioning refers to the identification and development of new uses for existing drugs and represents an alternative drug development strategy.In this work, we evaluated the antitumor effect of metronomic treatment with a combination of two repositioned drugs, metformin and propranolol, in triple negative breast cancer models.By in vitro studies with five different breast cancer derived cells, we observed that combined treatment decreased proliferation (P < 0.001), mitochondrial activity (P < 0.001), migration (P < 0.001) and invasion (P < 0.001). In vivo studies in immunocompetent mice confirmed the potential of this combination in reducing tumor growth (P < 0.001) and preventing metastasis (P < 0.05).Taken together our results suggest that metformin plus propranolol combined treatment might be beneficial for triple negative breast cancer control, with no symptoms of toxicity.
authors.affiliation: Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.|El Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.
authors.forename: María
authors.initials: M
authors.lastname: Rico
authors.affiliation: Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: María
authors.initials: M
authors.lastname: Baglioni
authors.affiliation: Aix-Marseille Université, Inserm UMR_S 911, Centre de Recherche en Oncologie biologique et Oncopharmacologie, Faculté de Pharmacie, Marseille, France.
authors.forename: Maryna
authors.initials: M
authors.lastname: Bondarenko
authors.affiliation: Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Nahuel Cesatti
authors.initials: NC
authors.lastname: Laluce
authors.affiliation: Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Viviana
authors.initials: V
authors.lastname: Rozados
authors.affiliation: Aix-Marseille Université, Inserm UMR_S 911, Centre de Recherche en Oncologie biologique et Oncopharmacologie, Faculté de Pharmacie, Marseille, France.|Service d'Hématologie and Oncologie Pédiatrique, AP-HM, Marseille, France.|Metronomics Global Health Initiative, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
authors.affiliation: Aix-Marseille Université, Inserm UMR_S 911, Centre de Recherche en Oncologie biologique et Oncopharmacologie, Faculté de Pharmacie, Marseille, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Carré
authors.affiliation: Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.|El Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.|Metronomics Global Health Initiative, Marseille, France.
authors.forename: O Graciela
authors.initials: OG
authors.lastname: Scharovsky
authors.affiliation: Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.|El Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Menacho Márquez
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D058492:Drug Repositioning; D004357:Drug Synergism; D004734:Energy Metabolism; D005260:Female; D006019:Glycolysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D001678:Organelle Biogenesis; D011433:Propranolol / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D008687:Metformin; D011433:Propranolol
keywords: breast cancer; drug repositioning; metformin; metronomics; propranolol