Histone deacetylase inhibitor: antineoplastic agent and radiation modulator.

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.