Histone deacetylase (HDAC) inhibitors are a group of anticancer drugs which cause growth arrest and apoptosis of several tumor cells. HDAC inhibitors have been also found to increase the anticancer efficacy of several treatment modalities i.e. chemotherapy or radiotherapy. Here, we review the literature on combinations of HDAC inhibitors both with ionizing radiation and with other drugs, highlighting DNA-damaging compounds. The results of numerous studies with several types of cancer cells discussed in this review demonstrate that HDAC inhibitors enhance the effect of DNA damaging agents, such as inhibitors of topoisomerases, inhibitors of DNA synthesis, DNA-intercalators and agents covalently modifying DNA (i.e. doxorubicin, etoposid, 5-fluorouracil, cisplatin, melphalan, temozolomide and ellipticine) or of irradiation. Hence, the use of HDAC inhibitors combined with these antitumor drugs or ionizing radiation is a promising tool which may make treatment of patients suffering from many types of cancer more efficient. Several molecular mechanisms are responsible for the observed higher sensitivity of tumor cells towards therapeutic agents elicited by HDAC inhibitors. These mechanisms are discussed also in this review.

Department of Biochemistry Faculty of Science Charles University Prague Czech Republic

Citace poskytuje Crossref.org

The Histone Deacetylase Inhibitor Valproic Acid Exerts a Synergistic Cytotoxicity with the DNA-Damaging Drug Ellipticine in Neuroblastoma Cells

Histone Deacetylase Inhibitors as Anticancer Drugs

The anticancer drug ellipticine activated with cytochrome P450 mediates DNA damage determining its pharmacological efficiencies: studies with rats, Hepatic Cytochrome P450 Reductase Null (HRN™) mice and pure enzymes