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Histone deacetylase inhibitor

    A '''HDAC inhibitor''' (HDI) is a class of drug which interfers with the function of histone deacetylase
    HDAC inhibitors are being studied as a treatment for cancer and neurodegenerative diseases The exact mechanisms by which the compounds may work are unclear but epigenetic pathways are proposed Richon et al Richon VM, Sandhoff TW, Rifkind RA, Marks PA. AUG 29 2000 "Histone deacetylase inhibitor selectively induces p21(WAF1) expression and gene-associated histone acetylation" Proceedings of the National Academy of Sciences of the States of America] 97(18):10014-10019 found that HDAC inhibitors can induce p21 (WAF1) expression a regulator of p53's tumor supressor activity el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. NOV 19 1993 "WAF1 a potential mediator of p53 tumor suppression" Cell 75(4):817-25 HDACs are involved in the pathway by which the retinoblastoma protein (pRb) suppresses cell proliferation The pRb protein is part of a complex which attracts HDACs to the chromatin so that it will deacetylate histonesBrehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T. 1998 Retinoblastoma protein recruits histone deacetylase to repress transcriptionNature 391(6667):597-601 HDAC1 negatively regulates the cardiovascular transcription factor Kruppel-like factor 5 through direct interaction Matsumura T, Suzuki T, Aizawa K, Munemasa Y, Muto S, Horikoshi M, Nagai R 2005 The deacetylase HDAC1 negatively regulates the cardiovascular transcription factor Kruppel-like factor 5 through direct interactionJ Bio ChemJ Bio Chem 280(13):12123-9 Estrogen is well-established as a mitogenic factor implicated in the tumorigenesis and progression of breast cancer via its binding to the estrogen receptor alpha (ERalpha) Recent data indicate that chromatin inactivation mediated by HDAC and DNA methylation is a critical component of ERalpha silencing in human breast cancer cells Zhang Z, Yamashita H, Toyama T, Sugiura H, Ando Y, Mita K, Hamaguchi M, Hara Y, Kobayashi S, Iwase H Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast2005 Breast Cancer Res TreatNov;94(1):11-6
    HDAC inhibitors are also associated with the inhibition of some gene promoters This could be due to increased activity of other negative-regulatory proteins however