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Metronomic metformin and propranolol combination prevents cancer progression and metastasis in breast cancer

María Rico, María Baglioni Maryna Bondarenko, Nahuel Cesatti Laluce, Viviana Rozados, Nicolas André, Manon Carré, O. Graciela Scharovsky, Mauricio Menacho Márquez from the Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina, the CONICET, the Aix-Marseille Université, Inserm UMR_S 911, Centre de Recherche en Oncologie biologique et Oncopharmacologie, Faculté de pharmacie, Marseille, France, the Service d’Hématologie and Oncologie Pédiatrique, AP-HM, Boulevard Jan Moullin, Marseille, France and the Metronomics Global Health Initiative, Marseille, Francehave just published in Oncotarget an article entitled : Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models

They report here that a combination of two repositioned drugs, namely Met and Prop, was able to slow down the growth of all the triple negative tumor cell lines and tumor-derived cells tested. They also were effective on the estrogen receptor (ER) positive MCF7 cells. Indeed, in all the cell types analyzed and regardless the method used, combination of Met+Prop showed a significantly stronger effect on cell growth than any individual drug. In fact, our in vitro data with 4T1 and MDA-MB-231 cells revealed that Met and Prop worked together in a synergistic manner blocking proliferation as it can be easily seen by the position of IC50 values falling below the additivity curve. Interestingly, the combination of these two drugs was effective not only to inhibit proliferation, but also to diminish the clonogenic capability and to increase apoptosis of the tumor cells.

Taken all together, these results indicate that the combination between Met and Prop is particularly effective in two different triple-negative, syngeneic breast cancer models, causing a significant metastasis-free prolonged survival with a favorable toxicity profile.

This strongly suggests the possibility of using these repositioned drugs combination for the treatment of triple-negative metastatic breast cancer. As a matter of fact, it would be extremely interesting to test the benefits of such a combination when using as an adjuvant treatment after surgery in order to prevent metastasis development and/or recurrences or even as a perioperative therapy during the surgical resection of tumors.

the fulltext version article is freely availalbe here