A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases Journal Article
| Authors: | Richon, V. M.; Emiliani, S.; Verdin, E.; Webb, Y.; Breslow, R.; Rifkind, R. A.; Marks, P. A. |
| Article Title: | A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases |
| Abstract: | Hybrid polar compounds (HPCs) have been synthesized that induce terminal differentiation and/or apoptosis in various transformed cells. We have previously reported on the development of the second-generation HPCs suberoylanilide hydroxamic acid (SAHA) and m-carboxycinnamic acid bishydroxamide (CBHA) that are 2,000-fold more potent inducers on a molar basis than the prototype HPC hexamethylene bisacetamide (HMBA). Herein we report that CBHA and SAHA inhibit histone deacetylase 1 (HDAC1) and histone deacetylase 3 (HDAC3) activity in vitro. Treatment of cells in culture with SAHA results in a marked hyperacetylation of histone H4, but culture with HMBA does not. Murine erythroleukemia cells developed for resistance to SAHA are cross-resistant to trichostatin A, a known deacetylase inhibitor and differentiation inducer, but are not cross-resistant to HMBA. These studies show that the second-generation HPCs, unlike HMBA, are potent inhibitors of HDAC activity. In this sense, HMBA and the second-generation HPCs appear to induce differentiation by different pathways. |
| Keywords: | unclassified drug; human cell; histone deacetylase inhibitor; nonhuman; animal cell; mouse; animals; mice; enzyme inhibition; cell differentiation; drug resistance; enzyme inhibitor; drug synthesis; urinary bladder neoplasms; animalia; cell transformation, neoplastic; cancer inhibition; cell transformation; carcinoma; immunoprecipitation; murinae; vorinostat; hydroxamic acids; cell line, transformed; histones; histone deacetylases; histone deacetylase; leukemia cell line; trichostatin a; acetylation; cinnamates; leukemia, erythroblastic, acute; hexamethylenebisacetamide; acetamides; humans; human; priority journal; article; 3 carboxycinnamic acid bishydroxamide; erythroleukemia cell; malonates |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 95 |
| Issue: | 6 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1998-03-17 |
| Start Page: | 3003 |
| End Page: | 3007 |
| Language: | English |
| DOI: | 10.1073/pnas.95.6.3003 |
| PUBMED: | 9501205 |
| PROVIDER: | scopus |
| PMCID: | PMC19684 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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