Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models
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María Rico1,2,*, María Baglioni1,*, Maryna Bondarenko3, Nahuel Cesatti Laluce1, Viviana Rozados1, Nicolas André3,4,5, Manon Carré3, O. Graciela Scharovsky1,2,5, Mauricio Menacho Márquez1,2
1Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina
2El Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina
3Aix-Marseille Université, Inserm UMR_S 911, Centre de Recherche en Oncologie biologique et Oncopharmacologie, Faculté de Pharmacie, Marseille, France
4Service d'Hématologie and Oncologie Pédiatrique, AP-HM, Marseille, France
5Metronomics Global Health Initiative, Marseille, France
*These authors contributed equally and are co-first authors
Mauricio Menacho Márquez, email: firstname.lastname@example.org
Keywords: breast cancer, metronomics, drug repositioning, metformin, propranolol
Received: July 22, 2016 Accepted: November 22, 2016 Published: December 01, 2016
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.
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