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

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

  • Exp Hematol Oncol. 2019 Nov 15;8:30. doi: 10.1186/s40164-019-0153-x.
Shanshan Zhang  # 1 2 3,  Zhaojian Gong  # 2 4,  Peter O Oladimeji  # 5,  Duane G Currier 5,  Qipan Deng 1 2,  Ming Liu 2 6,  Taosheng Chen 5,  Yong Li 1 2
Affiliations

Affiliations

  • 1 1Section of Epidemiology & Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX USA.
  • 2 2Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH USA.
  • 3 3Department of Stomatology, Xiangya Hospital, Central South University, Changsha, China.
  • 4 4Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, China.
  • 5 5Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN USA.
  • 6 6State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
  • # Contributed equally.
PMID: 31788346 DOI: 10.1186/s40164-019-0153-x
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.

Keywords

Dacinostat; HDAC inhibitors; High-throughput screening; Medulloblastoma; Quisinostat.

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