title: Histone deacetylase inhibitor: antineoplastic agent and radiation modulator.
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.
authors: Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20057-1482, USA.
authors: Zacharoula
authors: Z
authors: Konsoula
authors: Alfredo
authors: A
authors: Velena
authors: Rachel
authors: R
authors: Lee
authors: Anatoly
authors: A
authors: Dritschilo
authors: Mira
authors: M
authors: Jung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004249:DNA Damage; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D011836:Radiation Tolerance; D011837:Radiation-Protective Agents / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents