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We report that the histone deacetylase inhibitors, Trichostatin A and Suberoylanilide Hydroxamic Acid (SAHA), dramatically reduce cell viability and promote apoptosis in different drug\u2010resistant cells, affecting in a much lesser extent to their parental drug\u2010sensitive counterparts. The differential effects induced by Trichostatin A and SAHA between drug\u2010sensitive and drug\u2010resistant cells are reflected on the main characteristics of the resistant phenotype. Thus, reverse transcription\u2010PCR and Western immunoblots confirm that both histone deacetylase inhibitors promote endogenous down\u2010regulation of P\u2010glycoprotein, which is overexpressed in the drug\u2010resistant cells. Transfection of drug\u2010sensitive cells with the P\u2010glycoprotein cDNA ruled out the <jats:italic>a priori<\/jats:italic> possible association between apoptosis and down\u2010regulation of P\u2010glycoprotein induced by the histone deacetylase inhibitors. The results suggest a therapeutic potential of histone deacetylase inhibitors in the treatment of cancers with acquired resistance. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10998","type":"journal-article","created":{"date-parts":[[2003,2,20]],"date-time":"2003-02-20T14:04:54Z","timestamp":1045749894000},"page":"579-586","source":"Crossref","is-referenced-by-count":35,"title":["Susceptibility of multidrug resistance tumor cells to apoptosis induction by histone deacetylase inhibitors"],"prefix":"10.1002","volume":"104","author":[{"given":"Maria D.","family":"Castro\u2010Galache","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose A.","family":"Ferragut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor M.","family":"Barbera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Mart\u00edn\u2010Orozco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose M.","family":"Gonzalez\u2010Ros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Garcia\u2010Morales","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Saceda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,2,14]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-200009000-00011"},{"key":"e_1_2_6_3_2","first-page":"155","article-title":"Pharmacology of drugs that alter multidrug resistance in cancer","volume":"42","author":"Ford JM","year":"1990","journal-title":"Pharmacol Rev"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.62.070193.002125"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.36.040196.001113"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(92)90131-6"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/323728a0"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(99)01493-0"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.2.490.490"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.39.1.361"},{"key":"e_1_2_6_11_2","doi-asserted-by":"crossref","first-page":"18031","DOI":"10.1016\/S0021-9258(19)84675-6","article-title":"Modulation of the expression of a multidrug resistance gene (MDR1\/Pglycoprotein) by differentiating agents","volume":"264","author":"Mickley LA","year":"1989","journal-title":"J Biol Chem"},{"key":"e_1_2_6_12_2","first-page":"147","article-title":"Enhanced expression of the human multidrug resistance 1 gene in response to UV light irradiation","volume":"4","author":"Uchiumi T","year":"1993","journal-title":"Cell Growth Diff"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.20.11037"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1346476"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/38664"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81063-6"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(99)01536-6"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106699200"},{"key":"e_1_2_6_19_2","first-page":"4392","article-title":"Hybrid polar histone deacetylase inhibitor induces apoptosis 21 and CD95\/CD95 ligand expression in human neuroblastoma.","volume":"59","author":"Glick RD","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.3003"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.21.11295"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/35042612"},{"key":"e_1_2_6_23_2","first-page":"4377","article-title":"Transcriptional regulation of the MDR1 gene by histone acetyltransferase and deacetylase is mediated by NF\u2010Y. 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