{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T22:58:57Z","timestamp":1771023537983,"version":"3.50.1"},"reference-count":27,"publisher":"American Veterinary Medical Association (AVMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>Objective<\/jats:bold>\u2014To determine whether exposure of canine cancer cells to histone deacetylase (HDAC) inhibitors S(+)-<jats:italic>N<\/jats:italic>-hydroxy-4-(3-methyl-2-phenyl-butyrylamino)benzamide (OSU-HDAC42) or suberoylanilide hydroxamic acid (SAHA) results in increased histone acetylation and decreased cell viability and whether any changes in viability involve induction of apoptosis or alterations in progression of the cell cycle.<\/jats:p>\n<jats:p><jats:bold>Sample Population<\/jats:bold>\u20149 canine cancer cell lines.<\/jats:p>\n<jats:p><jats:bold>Procedures<\/jats:bold>\u2014Cells from 9 canine cancer cell lines were treated with dimethyl sulfoxide vehicle, OSU-HDAC42, or SAHA, then assays of cell viability were performed. Histone acetylation was assessed by use of western blot analysis. Apoptosis was assessed via ELISA to detect fragmentation of cytoplasmic nucleosomal DNA and western blot analysis to detect cleavage of caspase 3. Cell cycle analysis was performed by use of propidium iodide staining and flow cytometry.<\/jats:p>\n<jats:p><jats:bold>Results<\/jats:bold>\u2014Concentrations of OSU-HDAC42 and SAHA required to achieve 50% inhibition of cell viability (IC<jats:sub>50<\/jats:sub>) were reached in cells of 6 and 4 canine cancer cell lines, respectively, and ranged from approximately 0.4 to 1.3\u03bcM for OSU-HDAC42 and 0.6 to 4.8\u03bcM for SAHA. Cells from T-cell lymphoma, mast cell tumor, osteosarcoma, and histiocytic sarcoma lines were most sensitive to HDAC inhibition, with IC<jats:sub>50<\/jats:sub>s of &lt; 1\u03bcM for OSU-HDAC42 and &lt; 5\u03bcM for SAHA. Induction of apoptosis was indicated via cleavage of caspase 3 and increases in cytoplasmic nucleosomes and the subG<jats:sub>1<\/jats:sub> cell population.<\/jats:p>\n<jats:p><jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Micromolar concentrations of HDAC inhibitors OSU-HDAC42 and SAHA induced histone acetylation, cytotoxicity, and apoptosis in canine cancer cells. In general, OSU-HDAC42 was more potent than SAHA.<\/jats:p>","DOI":"10.2460\/ajvr.69.7.938","type":"journal-article","created":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T13:34:11Z","timestamp":1214919251000},"page":"938-945","source":"Crossref","is-referenced-by-count":27,"title":["Evaluation of the effects of histone deacetylase inhibitors on cells from canine cancer cell lines"],"prefix":"10.2460","volume":"69","author":[{"given":"William C.","family":"Kisseberth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sridhar","family":"Murahari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl A.","family":"London","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel 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