<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><p>Neuroblastoma, a tumor of the peripheral sympathetic nervous system, is the most frequent solid extra cranial tumor in children and is a major cause of death from neoplasia in infancy. Still little improvement in therapeutic options has been made, requiring a need for the development of new therapies. In our laboratory, we address still unsettled questions, which of mechanisms of action of DNA-damaging drugs both currently use for treatment of human neuroblastomas (doxorubicin, cis-platin, cyclophosphamide and etoposide) and another anticancer agent decreasing growth of neuroblastomas <italic>in vitro</italic>, ellipticine, are predominant mechanism(s) responsible for their antitumor action in neuroblastoma cell lines <italic>in vitro.</italic> Because hypoxia frequently occurs in tumors and strongly correlates with advanced disease and poor outcome caused by chemoresistance, the effects of hypoxia on efficiencies and mechanisms of actions of these drugs in neuroblastomas are also investigated. Since the epigenetic structure of DNA and its lesions play a role in the origin of human neuroblastomas, pharmaceutical manipulation of the epigenome may offer other treatment options also for neuroblastomas. Therefore, the effects of histone deacetylase inhibitors on growth of neuroblastoma and combination of these compounds with doxorubicin, cis-platin, etoposide and ellipticine as well as mechanisms of such effects in human neuroblastona cell lines <italic>in vitro</italic> are also investigated. Such a study will increase our knowledge to explain the proper function of these drugs on the molecular level, which should be utilized for the development of new therapies for neuroblastomas.</p></abstract>

Neuroblastoma, a tumor of the peripheral sympathetic nervous system, is the most frequent solid extra cranial tumor in children and is a major cause of death from neoplasia in infancy. Still little improvement in therapeutic options has been made, requiring a need for the development of new therapies. In our laboratory, we address still unsettled questions, which of mechanisms of action of DNA-damaging drugs both currently use for treatment of human neuroblastomas (doxorubicin, cis-platin, cyclophosphamide and etoposide) and another anticancer agent decreasing growth of neuroblastomas in vitro, ellipticine, are predominant mechanism(s) responsible for their antitumor action in neuroblastoma cell lines in vitro. Because hypoxia frequently occurs in tumors and strongly correlates with advanced disease and poor outcome caused by chemoresistance, the effects of hypoxia on efficiencies and mechanisms of actions of these drugs in neuroblastomas are also investigated. Since the epigenetic structure of DNA and its lesions play a role in the origin of human neuroblastomas, pharmaceutical manipulation of the epigenome may offer other treatment options also for neuroblastomas. Therefore, the effects of histone deacetylase inhibitors on growth of neuroblastoma and combination of these compounds with doxorubicin, cis-platin, etoposide and ellipticine as well as mechanisms of such effects in human neuroblastona cell lines in vitro are also investigated. Such a study will increase our knowledge to explain the proper function of these drugs on the molecular level, which should be utilized for the development of new therapies for neuroblastomas.

DNA and histone deacetylases as targets for neuroblastoma treatment

Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic

Department of Pediatric Hematology and Oncology, 2nd Medical School, Charles University and University Hospital Motol, Prague, Czech Republic

Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University of Agriculture and Forestry, Brno, Czech Republic

Division of Preventive Oncology, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany

Interdisciplinary Toxicology

{"article-title":"DNA and histone deacetylases as targets for neuroblastoma treatment"}

Neuroblastoma, a tumor of the peripheral sympathetic nervous system, is the most frequent solid extra cranial tumor in children and is a major cause of death...

DNA and histone deacetylases as targets for neuroblastoma treatment

Publié en ligne: 30 juil. 2010

Pages: 47 - 52

DOI: https://doi.org/10.2478/v10102-010-0010-6

Mots clés
neuroblastoma, DNA-damaging anticancer drugs, inhibitors of histone deacetylases, mechanisms of acticancer effects of drugs

This content is open access.

DNA and histone deacetylases as targets for neuroblastoma treatment

Publié en ligne: 30 juil. 2010

Pages: 47 - 52

DOI: https://doi.org/10.2478/v10102-010-0010-6

Mots clésneuroblastoma, DNA-damaging anticancer drugs, inhibitors of histone deacetylases, mechanisms of acticancer effects of drugs

This content is open access.

Mots clés
neuroblastoma, DNA-damaging anticancer drugs, inhibitors of histone deacetylases, mechanisms of acticancer effects of drugs