Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line

Anaplastic thyroid carcinoma (ATC) is a very aggressive human malignancy, having a marked degree of invasiveness and no features of thyroid differentiation. It is known that either HDAC inhibitors or PARP inhibitors have antiproliferative effects on thyroid cancer cells. Therefore, in this study the...

Full description

Saved in:
Bibliographic Details
Main Authors: Federica Baldan, Catia Mio, Lorenzo Allegri, Cinzia Puppin, Diego Russo, Sebastiano Filetti, Giuseppe Damante
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2015/978371
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850159235794468864
author Federica Baldan
Catia Mio
Lorenzo Allegri
Cinzia Puppin
Diego Russo
Sebastiano Filetti
Giuseppe Damante
author_facet Federica Baldan
Catia Mio
Lorenzo Allegri
Cinzia Puppin
Diego Russo
Sebastiano Filetti
Giuseppe Damante
author_sort Federica Baldan
collection DOAJ
description Anaplastic thyroid carcinoma (ATC) is a very aggressive human malignancy, having a marked degree of invasiveness and no features of thyroid differentiation. It is known that either HDAC inhibitors or PARP inhibitors have antiproliferative effects on thyroid cancer cells. Therefore, in this study the possible synergy between the two types of compounds has been investigated. The 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-specific 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.
format Article
id doaj-art-b0fbff6418d946359ecb64ddb98c0be4
institution OA Journals
issn 1687-8337
1687-8345
language English
publishDate 2015-01-01
publisher Wiley
record_format Article
series International Journal of Endocrinology
spelling doaj-art-b0fbff6418d946359ecb64ddb98c0be42025-08-20T02:23:36ZengWileyInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/978371978371Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell LineFederica Baldan0Catia Mio1Lorenzo Allegri2Cinzia Puppin3Diego Russo4Sebastiano Filetti5Giuseppe Damante6Department of Medical and Biological Sciences, University of Udine, Piazzale Kolbe 4, 33100 Udine, ItalyDepartment of Medical and Biological Sciences, University of Udine, Piazzale Kolbe 4, 33100 Udine, ItalyDepartment of Medical and Biological Sciences, University of Udine, Piazzale Kolbe 4, 33100 Udine, ItalyDepartment of Medical and Biological Sciences, University of Udine, Piazzale Kolbe 4, 33100 Udine, ItalyDepartment of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, ItalyDepartment of Internal Medicine and Medical Specialties, University of Roma “La Sapienza”, 00198 Rome, ItalyDepartment of Medical and Biological Sciences, University of Udine, Piazzale Kolbe 4, 33100 Udine, ItalyAnaplastic thyroid carcinoma (ATC) is a very aggressive human malignancy, having a marked degree of invasiveness and no features of thyroid differentiation. It is known that either HDAC inhibitors or PARP inhibitors have antiproliferative effects on thyroid cancer cells. Therefore, in this study the possible synergy between the two types of compounds has been investigated. The 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-specific 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.http://dx.doi.org/10.1155/2015/978371
spellingShingle Federica Baldan
Catia Mio
Lorenzo Allegri
Cinzia Puppin
Diego Russo
Sebastiano Filetti
Giuseppe Damante
Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line
International Journal of Endocrinology
title Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line
title_full Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line
title_fullStr Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line
title_full_unstemmed Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line
title_short Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line
title_sort synergy between hdac and parp inhibitors on proliferation of a human anaplastic thyroid cancer derived cell line
url http://dx.doi.org/10.1155/2015/978371
work_keys_str_mv AT federicabaldan synergybetweenhdacandparpinhibitorsonproliferationofahumananaplasticthyroidcancerderivedcellline
AT catiamio synergybetweenhdacandparpinhibitorsonproliferationofahumananaplasticthyroidcancerderivedcellline
AT lorenzoallegri synergybetweenhdacandparpinhibitorsonproliferationofahumananaplasticthyroidcancerderivedcellline
AT cinziapuppin synergybetweenhdacandparpinhibitorsonproliferationofahumananaplasticthyroidcancerderivedcellline
AT diegorusso synergybetweenhdacandparpinhibitorsonproliferationofahumananaplasticthyroidcancerderivedcellline
AT sebastianofiletti synergybetweenhdacandparpinhibitorsonproliferationofahumananaplasticthyroidcancerderivedcellline
AT giuseppedamante synergybetweenhdacandparpinhibitorsonproliferationofahumananaplasticthyroidcancerderivedcellline