Propranolol potentiates the anti-angiogenic effects and antitumor efficacy of chemotherapy agents: Implication in breast cancer treatment

Eddy Pasquier 1,5 , Joseph Ciccolini 2 , Manon Carre 3 , Sarah Giacometti 2 , Raphaelle Fanciullino 2 , Charlotte Pouchy 1,‡ , Marie-Pierre Montero 3 , Cindy Serdjebi 2 , Maria Kavallaris 1 and Nicolas Andre 3,4,5 1 Children’s Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia 2 Pharmacokinetics Unit, UMR-MD3, Aix-Marseille Univ, Marseille, France 3 INSERM UMR 911, Centre de Recherche en Oncologie biologique et en Oncopharmacologie, Aix-Marseille Univ, Marseille, France 4 Hematology & Pediatric Oncology Department, La Timone University Hospital of Marseille, France 5 Metronomics Global Health Initiative, Marseille, France ‡ Current Address: Universite Pierre et Marie Curie - Univ Paris 6, CNRS UMR 7211, INSERM U959, Paris, France Received: October 13, 2011; Accepted: October 14, 2011; Published: October 17, 2011; Keywords: breast cancer, angiogenesis, propranolol, beta-adrenergic receptor antagonist, chemotherapy, combination therapy Correspondence: Eddy Pasquier, PhD, email: // Nicolas Andre, MD, PhD, email: // // Abstract Recent clinical evidence revealed that the use of beta-blockers such as propranolol, prior to diagnosis or concurrently with chemotherapy, could increase relapse-free and overall survival in breast cancer patients. We therefore hypothesized that propranolol may be able to increase the efficacy of chemotherapy either through direct effects on cancer cells or via anti-angiogenic mechanisms. In vitro proliferation assay showed that propranolol (from 50-100 μM) induces dose-dependent anti-proliferative effects in a panel of 9 human cancer and “normal” cell lines. Matrigel assays revealed that propranolol displays potent anti-angiogenic properties at non-toxic concentrations (