Drug repurposing of β-blocker propranolol in osteosarcoma: preclinical antitumor efficacy on 2D/3D cell growth, chemotaxis and xenograft progression, alone or in combination with standard-of-care chemotherapy

SOLERNÓ LM; SOBOL NT; RODRÍGUEZ RB; PIFANO M; RIPOLL GV; ALONSO DF; GARONA J

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia 2019; 2019

Sociedad Argentina de Investigación Clínica

Introduction.Osteosarcoma (OS), a bone cancer which primarily affects adolescents and young adults, is considered a clinical challenge due to its aggressiveness, rapid progression and limited response to standard of care therapies (SoC) such as cisplatin and methotrexate. Propranolol (PPN) is a non-selective β-adrenergic receptor (β-AR) antagonist originally used in the treatment of diverse heart diseases. Given that β-AR signalling regulates many cellular processes involved in the initiation and progression of cancer, multiple efforts have been made to repurpose PPN in indications such as breast cancer, melanoma and angiosarcoma.Objectives and experimental design.Considering the unsatisfied clinical needs of OS, the objective of this work was to evaluate the in vitro/in vivo antitumoral activity of PPN as a monotherapy and/or in combination with SoC chemotherapy, in highly aggressive MG-63 and U-2OS human OS cells. Results.PPN blocked promitogenic β-AR activation by catecholamines in OS cells and drastically reduced clonogenic growth, chemotaxis and proliferation of exponentially-growing OS cells (IC50= 45 µM; p