Inhibitors of the histone deacetylases (HDACIs), a class of small molecules primarily involved in the modification of epigenetic regulation, have been exploited widely for their anti-cancer effects and/or chemo/ radio-sensitization properties. The mechanisms of action of several HDACIs have been unraveled that include modifications of histone acetylation status influencing gene expression and/or changes in the post-translational modifications of proteins that collectively result in alterations in vital cell functions like proliferation, differentiation, death (apoptosis) and senescence manifesting in differential responses between pathological (cancer and others) and normal tissues (and cells). Reason for HDACI becoming the choice for anticancer therapeutics is their excellent differential action on normal and cancer cells at the therapeutic dosages. Some HDACIs like Zolinza (vorinostat or SAHA) and depsipeptide (Romidepsin or FK228) have been granted FDA approval for the treatment of various cancer types and many are at pre-clinical and clinical trial stages. Some of the non-oncologic effects have however unfolded interesting properties of HDACIs like cyto and neuroprotection, antiinflammatory and radioprotective actions and indicated the possible applications of HDACIs in the treatment of nononcologic diseases like asthma, arthritis and other autoimmune disorders, neurodegeneration, diabetes, muscular dystrophy, bone marrow transplantation etc. We briefly review the current status of the applications of HDAC inhibitors in oncology and non-oncological diseases and the possibilities of developing them as radiation countermeasure agents, especially as mitigators of radiation injury.
Keywords: Epigenetic, HDAC inhibitor, radiosensitizer, radiation countermeasure