Identification of novel small-molecule inhibitors of glioblastoma cell growth and invasion by high-throughput screening

Abstract

Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor with a very poor prognosis. Current therapies for GBM remain palliative and advances made in decades have resulted in only a slight improvement in treatment outcome. Exploring new therapeutic agents for GBM treatment, therefore, is of prime importance. In the present study, we performed a high-throughput screening for GBM cell growth and invasion, with an attempt to identify novel potential anti-GBM agents. An annotated compound library (LOPAC1280) of 1,280 pharmacologically active compounds was screened and ten compounds were validated and identified as inhibitors of GBM cell growth and invasion. Four of them, i.e., 6-nitroso-1,2-benzopyrone, S-(p-azidophenacyl) glutathione, phenoxybenzamine hydrochloride, and SCH-28080 have not been implicated in GBM cell growth and invasion previously, suggesting that they may serve as novel potential therapeutic agents for GBM treatment. In conclusion, novel inhibitors of GBM cell growth and invasion were identified in the present study, which provides a basis for the development of therapies for GBM, and may shed light on the molecular mechanisms underlying GBM cell behavior.