Novel repurposing of propranolol as an anti-tumor agent in glioblastoma

Authors

• MJ Shepard
• A Bugarini
• Q Zhang
• Z Zhuang
• P Chittiboina

Abstract

Introduction Glioblastoma (GBM) is the most common and uniformly fatal malignant brain tumor. Despite improved understanding of its pathogenesis, survivorship rates remain poor, underscoring the need for novel anti-tumor strategies. Propranolol is a beta-1/beta-2 adrenergic-receptor (BAR/BAR2) antagonist used for treatment of hypertension. Propranolol was discovered to have anti-tumor effects in infantile hemangiomas, thought to be due to inverse-agonism of BARs leading to decreased intracellular levels of cAMP. Preclinical studies suggest broad anti-tumor activity of propranolol against other solid tumors. We investigated whether propranolol may have a role in the treatment of GBM. Methods Four GBM cell lines (U251/GL261/S635 and 9L) were cultured and treated with propranolol. Viability assays, QT-PCR, flow-cytometry, migration assays and western blot analysis were performed using clinically relevant concentrations of propranolol. RNAi was used to determine the dependency of propranolol anti-tumor activity on BAR1 and BAR2 expression. Results Treatment with propranolol reduced GBM viability with an IC50 of 100uM 24-hours post-exposure. Treated cells demonstrated a 6-fold reduction in migratory capacity and increased rates of apoptosis (p

Scientific Focus Area: Cancer Biology

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