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Updated: Jan 2, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
A high-throughput screening identifies histone deacetylase inhibitors as therapeutic agents against medulloblastoma
Shanshan Zhang1,2,3, Zhaojian Gong2,4, Peter O Oladimeji5
11Section of Epidemiology & Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX USA.
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.
Insights
Histone deacetylase inhibitors like dacinostat and quisinostat show promise in treating medulloblastoma, a common childhood brain cancer. These compounds effectively reduced tumor growth and cancer cell proliferation in preclinical studies.
Area of Science:
- Pediatric oncology
- Cancer biology
- Pharmacology
Background:
- Medulloblastoma is the most common malignant pediatric brain tumor.
- Current treatments (surgery, radiation, chemotherapy) have limitations and severe side effects.
- Effective and less toxic therapeutic strategies for medulloblastoma are needed.
Purpose of the Study:
- To identify novel drug candidates with anti-proliferative effects on medulloblastoma cells.
- To evaluate the efficacy of identified compounds in preclinical medulloblastoma models.
Main Methods:
- Conducted a high-throughput cell viability screen of 12,800 compounds.
- Assessed anti-proliferative and cytotoxic effects on medulloblastoma cell lines.
- Evaluated tumor growth inhibition in mouse xenograft models.
Main Results:
- Identified two histone deacetylase inhibitors, dacinostat and quisinostat, with significant anti-proliferative activity.
- Demonstrated that these compounds induce cytotoxicity, apoptosis, and cell cycle arrest (G2/M phase).
- Showed that dacinostat and quisinostat attenuated medulloblastoma tumor growth in vivo.
Conclusions:
- Histone deacetylase inhibitors represent a promising therapeutic class for medulloblastoma.
- Dacinostat and quisinostat warrant further investigation as potential treatments for medulloblastoma.
