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Human Cell Transformation pp 171–179Cite as

Histone Deacetylase Inhibitor: Antineoplastic Agent and Radiation Modulator

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 720))

Abstract

Inhibitors of histone deacetylases (HDACs) have emerged as a new class of anticancer agents based on their actions in cancer cell growth and cell cycle arrest, terminal differentiation, and apoptosis. Previously, we rationally designed and developed a new class of hydroxamide- and mercaptoacetamide-bearing HDAC inhibitors. A subset of these inhibitors exhibited chemo-radiation sensitizing properties in various human cancer cells. Furthermore, some HDAC inhibitors protected normal cells from radiation-induced damage and extended the survival of mice following total body exposure to lethal dose radiation. Pathological analyses revealed that intestinal and bone marrow cellularities recovered significantly from radiation-induced damage by structural compartments restoration, suggesting the mechanism of action of these HDAC inhibitors. These findings support the hypothesis that epigenetic regulation may play a crucial role in the functional recovery of normal tissues from radiation injuries.

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Acknowledgments

We thank S. Lee and J. Tuturea for technical support. This work was supported in part by USMRC grants PC030471 (M. Jung) as well as the Lombardi Comprehensive Cancer Center Microscopy and Imaging Shared Resource, US Public Health Service Grant 2P30-CA-51008 and 1S10 RR15768-01.

Author information

Authors and Affiliations

  1. Department of Radiation Medicine, The Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, N.W, 571482, Washington, DC, 20057-1482, USA

    Zacharoula Konsoula, Alfredo Velena, Rachel Lee, Anatoly Dritschilo & Mira Jung

  2. Departments of Oncology and Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA

    Anatoly Dritschilo

Authors
  1. Zacharoula Konsoula
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  2. Alfredo Velena
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  3. Rachel Lee
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  4. Anatoly Dritschilo
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  5. Mira Jung
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Corresponding author

Correspondence to Mira Jung .

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Editors and Affiliations

  1. Uniformed Services, Department of Surgery, University of the Health Sciences, South Glen Road 11455, Bethesda, 20854, Maryland, USA

    Johng S. Rhim

  2. , Department of Medicine, McGill University Health Centre, Pine Ave 687, Montreal, Québec, Canada

    Richard Kremer

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Konsoula, Z., Velena, A., Lee, R., Dritschilo, A., Jung, M. (2011). Histone Deacetylase Inhibitor: Antineoplastic Agent and Radiation Modulator. In: Rhim, J., Kremer, R. (eds) Human Cell Transformation. Advances in Experimental Medicine and Biology, vol 720. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0254-1_14

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