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

Federica Baldan,Giuseppe Damante,Diego Russo,Catia Mio,Lorenzo Allegri,Cinzia Puppin,Sebastiano Filetti

doi:10.1155/2015/978371

Abstract

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.

Highlights

Thyroid cancer is the most common endocrine malignancy, and its incidence has continuously increased in the last three decades all over the world [1]
The Anaplastic thyroid carcinoma (ATC)-derived cell line SW1736 has been treated with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and the poly(ADP-ribose) polymerases (PARPs) inhibitor PJ34, alone or in combination
We investigated the possible use of SAHA, an HDAC inhibitor, and PJ34, a PARP inhibitor, in combination, in a cellular model of anaplastic thyroid cancer

Summary

Introduction

Thyroid cancer is the most common endocrine malignancy, and its incidence has continuously increased in the last three decades all over the world [1]. Thyroid cancers are typically classified as papillary (PTC), follicular (FTC), medullary (MTC), or anaplastic (ATC) carcinomas. ATC is one of the most aggressive human malignancies. These tumors have a marked degree of invasiveness and extensive necrosis and there are no features of thyroid differentiation [2]. Patients with ATC still have a median survival of 5 months and less than 20% survive 1 year. Early tumor dissemination results in 20–50% percent of patients having distant metastases and 90% having adjacent tissue invasion on presentation [2]

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Conclusion