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.

Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line / Baldan, Federica; Mio, Catia; Allegri, Lorenzo; Puppin, Cinzia; Russo, Diego; Filetti, Sebastiano; Damante, Giuseppe. - In: INTERNATIONAL JOURNAL OF ENDOCRINOLOGY. - ISSN 1687-8337. - ELETTRONICO. - 2015:(2015), p. 978371. [10.1155/2015/978371]

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

FILETTI, SEBASTIANO;
2015

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.
2015
Endocrine and Autonomic Systems; Endocrinology; thyroid carcinoma; anaplastic thyroid carcinoma
01 Pubblicazione su rivista::01a Articolo in rivista
Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line / Baldan, Federica; Mio, Catia; Allegri, Lorenzo; Puppin, Cinzia; Russo, Diego; Filetti, Sebastiano; Damante, Giuseppe. - In: INTERNATIONAL JOURNAL OF ENDOCRINOLOGY. - ISSN 1687-8337. - ELETTRONICO. - 2015:(2015), p. 978371. [10.1155/2015/978371]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/887380
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