Research Article Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line Federica Baldan, 1 Catia Mio, 1 Lorenzo Allegri, 1 Cinzia Puppin, 1 Diego Russo, 2 Sebastiano Filetti, 3 and Giuseppe Damante 1,4 1 Department of Medical and Biological Sciences, University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy 2 Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy 3 Department of Internal Medicine and Medical Specialties, University of Roma “La Sapienza”, 00198 Rome, Italy 4 Institute of Medical Genetics, University Hospital “S. Maria della Misericordia”, 33100 Udine, Italy Correspondence should be addressed to Giuseppe Damante; giuseppe.damante@uniud.it Received 3 June 2014; Accepted 9 September 2014 Academic Editor: Ginesa Garc´ ıa-Rost´ an Copyright © 2015 Federica Baldan et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Anaplastic thyroid carcinoma (ATC) is a very aggressive human malignancy, having a marked degree of invasiveness and no features of thyroid diferentiation. It is known that either HDAC inhibitors or PARP inhibitors have antiproliferative efects on thyroid cancer cells. herefore, in this study the possible synergy between the two types of compounds has been investigated. he ATC-derived cell line SW1736 has been treated with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and the PARP inhibitor PJ34, alone or in combination. In terms of cell viability, the combination index value was always lower than 1 at various tested dosages, indicating, therefore, synergy in a wide range of doses for both compounds. Synergy was also observed in induction of apoptosis. In terms of thyroid-speciic gene expression, synergy was observed for TSHR mRNA levels but not for NIS, TTF1, TTF2, and PAX8 mRNA levels. Altogether, these data suggest that the combined use of HDAC and PARP inhibitors may be a useful strategy for treatment of ATC. 1. Introduction hyroid cancer is the most common endocrine malignancy, and its incidence has continuously increased in the last three decades all over the world [1]. hyroid cancers are typically classiied as papillary (PTC), follicular (FTC), medullary (MTC), or anaplastic (ATC) carcinomas. ATC is one of the most aggressive human malignancies. hese tumors have a marked degree of invasiveness and extensive necrosis and there are no features of thyroid difer- entiation [2]. he mechanisms underlying the development of ATCs are incompletely understood. Currently, available therapy for ATCs includes chemotherapy, radiotherapy, and surgery [3]. Nonetheless, patients with ATC still have a median survival of 5 months and less than 20% survive 1 year. Furthermore early tumor dissemination results in 20–50% percent of patients having distant metastases and 90% having adjacent tissue invasion on presentation [2]. HDAC inhibitors (HDACIs) are a group of small mole- cules that promote gene transcription by chromatin remod- eling and have been extensively studied as potential drugs for treating cancer. Luong et al. have established that the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), already FDA-approved for the treatment of several neoplastic diseases [4, 5], has antitumor activities against thyroid cancer [6]. Inhibitors of the poly(ADP-ribose) polymerases (PARPs) family are currently being evaluated as potential anticancer drugs. PARPs have a key role in a large number of cell viability processes as DNA repair, genome integrity, regulation of transcription, proliferation, and apoptosis [7]. Diferent independent studies have demonstrated that the combination of both HDAC inhibitors and PARP inhibitors with other drugs could result in synergistic efects on their antitumor activities if compared to those observed using single agents [8, 9]. Hindawi Publishing Corporation International Journal of Endocrinology Volume 2015, Article ID 978371, 7 pages http://dx.doi.org/10.1155/2015/978371