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


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.

SUBMITTER: Zhang S 

PROVIDER: S-EPMC6858705 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Zhang Shanshan S   Gong Zhaojian Z   Oladimeji Peter O PO   Currier Duane G DG   Deng Qipan Q   Liu Ming M   Chen Taosheng T   Li Yong Y  

Experimental hematology & oncology 20191115


<h4>Background</h4>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.<h4>Methods</h4>In this study, we employed a high-throughput cell viability assay to screen 12,800 compounds and to identify drug candida  ...[more]

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