A high-throughput screening identifies histone deacetylase inhibitors as therapeutic agents against medulloblastoma

Published on 2019-11-16T05:19:12Z (GMT) by
Abstract Background Medulloblastoma is the most frequently occurring malignant brain tumor in children. Current treatment strategies for medulloblastoma include aggressive surgery, cranio-spinal irradiation and adjuvant chemotherapy. Because current treatments can cause severe long-term side effects and are not curative, successful treatment remains a challenge. Methods In this study, we employed a high-throughput cell viability assay to screen 12,800 compounds and to identify drug candidates with anti-proliferative properties for medulloblastoma cells. We also tested these compounds for attenuating medulloblastoma tumor development using mouse xenografts. Results We identified two histone deacetylase inhibitors (dacinostat and quisinostat) with anti-proliferative properties for medulloblastoma cells. We showed that both compounds induce cytotoxicity, trigger cell apoptosis, and block cell cycle progression at the G2/M phase. In addition, dacinostat and quisinostat attenuated xenograft medulloblastoma growth in mice. Conclusions Our findings suggest that histone deacetylase inhibitors are potent therapeutic agents against medulloblastoma.

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Zhang, Shanshan; Gong, Zhaojian; Oladimeji, Peter; Currier, Duane; Deng, Qipan; Liu, Ming; et al. (2019): A high-throughput screening identifies histone deacetylase inhibitors as therapeutic agents against medulloblastoma. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4741862.v1