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There is an urgent need to explore new and better therapeutic strategies. We have previously described a family of Microtubule Destabilizing Sulfonamides (MDS) that does not trigger multidrug-mediated resistance in OC cell lines. MDS bind to the colchicine site of tubulin, disrupting the microtubule network and causing antiproliferative and cytotoxic effects. In this work, a novel microtubule-destabilizing agent (PILA9) was synthetized and characterized. This compound also inhibited OC cell proliferation and induced G2\/M cell cycle arrest and apoptosis. Interestingly, PILA9 was significantly more cytotoxic than MDS. Here, we also analyzed the effect of these microtubule-destabilizing agents (MDA) in combination with Panobinostat, a pan-histone deacetylase inhibitor. We found that Panobinostat synergistically enhanced MDA-cytotoxicity. Mechanistically, we observed that Panobinostat and MDA induced \u03b1-tubulin acetylation and that the combination of both agents enhanced this effect, which could be related to the observed synergy. Altogether, our results suggest that MDA\/Panobinostat combinations could represent new therapeutic strategies against OC.<\/jats:p>","DOI":"10.3390\/ijms232113019","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T20:37:58Z","timestamp":1666903078000},"page":"13019","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Panobinostat Synergistically Enhances the Cytotoxicity of Microtubule Destabilizing Drugs in Ovarian Cancer Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-9491","authenticated-orcid":false,"given":"Mar\u00eda","family":"Ovejero-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Molecular Medicine Unit, Department of Medicine, University of Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Asensio-Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Laboratorio de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Ciencias Farmac\u00e9uticas, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2623-1256","authenticated-orcid":false,"given":"Pilar","family":"Puebla","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Laboratorio de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Ciencias Farmac\u00e9uticas, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5943-3220","authenticated-orcid":false,"given":"Miguel","family":"Vicente-Manzanares","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1433-1612","authenticated-orcid":false,"given":"Rafael","family":"P\u00e9laez","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Laboratorio de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Ciencias Farmac\u00e9uticas, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2726-6795","authenticated-orcid":false,"given":"Rogelio","family":"Gonz\u00e1lez-Sarmiento","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Molecular Medicine Unit, Department of Medicine, University of Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1414-6532","authenticated-orcid":false,"given":"Ana Bel\u00e9n","family":"Herrero","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Molecular Medicine Unit, Department of Medicine, University of Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of 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