Non-cancer uses of histone deacetylase inhibitors: effects on infectious diseases and beta-hemoglobinopathies.
After the approval of suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) for the treatment of cutaneous T cell lymphoma (CTCL), a number of HDAC inhibitors (HDACi) are currently in Phase II or III clinical trials (alone or in combination) for the treatment of a great number of tumors. In addition to these cancer uses, HDACi can be successfully used in non-cancer diseases. In this review we focused on the uses of HDACi in some infectious diseases and beta-hemoglobinopaties. In C. albicans cultures, HDACi increased the frequency of cell switching (a relevant virulence trait) in the white-to-opaque transition, reduced the azole trailing effect through reduction in azole-dependent upregulation of CDR and ERG genes, and inhibited the fluconazole-dependent resistance induction. Moreover, they inhibited germination in several strains, and caused 90% reduction in the adherence of C. albicans to human cultured pneumocytes. In HIV-1-infected cells, the treatment with HDACi reactivates the HIV-1 expression in latent cellular reservoirs. Thus, the use of HDACi as adjuvant to highly active antiretroviral therapy (HAART) can represent a new potential therapeutic strategy to eradicate the viral infection. A number of HDACi have been reported as active against P. falciparum infection. Two recent papers show some 2-aminosuberic acid-based compounds as well as a series of phenylthiazolyl suberoyl hydroxamates as very potent and selective antimalarial agents. Among the many agents capable to perform post-natal reactivation of fetal hemoglobin production, HDACi for their capacity to de-repress gamma-globin gene expression in adult red cell, are presently considered promising molecules for personalized therapy of beta-hemoglobinopathies.
Rotili
Dante
D
Pasteur Institute, Cenci-Bolognetti Foundation, Department of Drug Chemistry and Technologies, Sapienza University of Rome, P. le A. Moro, 5, 00185, Rome, Italy.
Simonetti
Giovanna
G
Savarino
Andrea
A
Palamara
Anna T
AT
Migliaccio
Anna R
AR
Mai
Antonello
A
D004358:Drug Therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006453:Hemoglobinopathies / Q000188:drug therapy; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007239:Infections / Q000188:drug therapy; D008288:Malaria / Q000188:drug therapy
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors