Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor

Rasa Zarnegar, Laurent Brunaud, Hajima Kanauchi, Mariwil Wong, Mami Fung, David Ginzinger, Quan Yang Duh, Orlo H. Clark, Barbara K. Kinder, Martha A. Zeiger, Andreas Zielke

Research output: Contribution to journalArticle

Abstract

Background. Radioactive iodine is used to identify and treat recurrent and metastatic thyroid cancer of follicular cell origin. Between 30% and 40% of thyroid cancers are either resistant or become resistant to sadioactive iodine. Increased sodium-iodide symporter (NIS) and decreased Pendrin (PDS) activity may be associated with increased radioactive iodine effectiveness. In this investigation the effects of Trichostatin A (TSA), a histone deacetylating inhibitor, on human thyroid NIS and PDS gene expression was investigated. Method. Cell lines from papillary, Hürthle, and follicular cell carcinomas were treated with TSA for 72 hours at concentrations up to 100 ng/mL. NIS and PDS gene expression was determined using quantitative RT-polymerase chain reaction. Results. NIS messenger RNA expression in cell carcinomas was increased 107- (1.8-307) and 217- (5.7-408) fold in papillary, 39- (20-63) and 58- (37-80) fold in Hürthle, and 459- (178-810) and 781- (412-1229) fold in follicular after treatment with 50 and 100 ng/mL of TSA, respectively. PDS messenger RNA expression in cell carcinomas was decreased 0.22- (0.05-0.45) and 0.27- (0.09-0.47) fold in papillary, 0.53- (0.46-0.60) and 0.54- (0.44-0.64) fold in Hürthle, and 0.32- (0.26-0.39) and 0.56- (0.47-0.64) fold in follicular, after the same treatment. Conclusions. In thyroid cancer cell lines, TSA dramatically increased NIS gene expression and reduced PDS expression. The increased NIS expression and reduced PDS expression may make radioiodine therapy more effective in patients with thyroid cancer, especially when the tumors have no or low uptake of radioiodine.

Original languageEnglish (US)
Pages (from-to)984-990
Number of pages7
JournalSurgery
Volume132
Issue number6
DOIs
StatePublished - Dec 1 2002
Externally publishedYes

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trichostatin A
Histone Deacetylase Inhibitors
Thyroid Neoplasms
Iodine
Carcinoma
Gene Expression
Cell Line
Messenger RNA
Therapeutics
Histones
Thyroid Gland
Polymerase Chain Reaction
Neoplasms

ASJC Scopus subject areas

  • Surgery

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Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor. / Zarnegar, Rasa; Brunaud, Laurent; Kanauchi, Hajima; Wong, Mariwil; Fung, Mami; Ginzinger, David; Duh, Quan Yang; Clark, Orlo H.; Kinder, Barbara K.; Zeiger, Martha A.; Zielke, Andreas.

In: Surgery, Vol. 132, No. 6, 01.12.2002, p. 984-990.

Research output: Contribution to journalArticle

Zarnegar, R, Brunaud, L, Kanauchi, H, Wong, M, Fung, M, Ginzinger, D, Duh, QY, Clark, OH, Kinder, BK, Zeiger, MA & Zielke, A 2002, 'Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor', Surgery, vol. 132, no. 6, pp. 984-990. https://doi.org/10.1067/msy.2002.128690
Zarnegar, Rasa ; Brunaud, Laurent ; Kanauchi, Hajima ; Wong, Mariwil ; Fung, Mami ; Ginzinger, David ; Duh, Quan Yang ; Clark, Orlo H. ; Kinder, Barbara K. ; Zeiger, Martha A. ; Zielke, Andreas. / Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor. In: Surgery. 2002 ; Vol. 132, No. 6. pp. 984-990.
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abstract = "Background. Radioactive iodine is used to identify and treat recurrent and metastatic thyroid cancer of follicular cell origin. Between 30{\%} and 40{\%} of thyroid cancers are either resistant or become resistant to sadioactive iodine. Increased sodium-iodide symporter (NIS) and decreased Pendrin (PDS) activity may be associated with increased radioactive iodine effectiveness. In this investigation the effects of Trichostatin A (TSA), a histone deacetylating inhibitor, on human thyroid NIS and PDS gene expression was investigated. Method. Cell lines from papillary, H{\"u}rthle, and follicular cell carcinomas were treated with TSA for 72 hours at concentrations up to 100 ng/mL. NIS and PDS gene expression was determined using quantitative RT-polymerase chain reaction. Results. NIS messenger RNA expression in cell carcinomas was increased 107- (1.8-307) and 217- (5.7-408) fold in papillary, 39- (20-63) and 58- (37-80) fold in H{\"u}rthle, and 459- (178-810) and 781- (412-1229) fold in follicular after treatment with 50 and 100 ng/mL of TSA, respectively. PDS messenger RNA expression in cell carcinomas was decreased 0.22- (0.05-0.45) and 0.27- (0.09-0.47) fold in papillary, 0.53- (0.46-0.60) and 0.54- (0.44-0.64) fold in H{\"u}rthle, and 0.32- (0.26-0.39) and 0.56- (0.47-0.64) fold in follicular, after the same treatment. Conclusions. In thyroid cancer cell lines, TSA dramatically increased NIS gene expression and reduced PDS expression. The increased NIS expression and reduced PDS expression may make radioiodine therapy more effective in patients with thyroid cancer, especially when the tumors have no or low uptake of radioiodine.",
author = "Rasa Zarnegar and Laurent Brunaud and Hajima Kanauchi and Mariwil Wong and Mami Fung and David Ginzinger and Duh, {Quan Yang} and Clark, {Orlo H.} and Kinder, {Barbara K.} and Zeiger, {Martha A.} and Andreas Zielke",
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T1 - Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor

AU - Zarnegar, Rasa

AU - Brunaud, Laurent

AU - Kanauchi, Hajima

AU - Wong, Mariwil

AU - Fung, Mami

AU - Ginzinger, David

AU - Duh, Quan Yang

AU - Clark, Orlo H.

AU - Kinder, Barbara K.

AU - Zeiger, Martha A.

AU - Zielke, Andreas

PY - 2002/12/1

Y1 - 2002/12/1

N2 - Background. Radioactive iodine is used to identify and treat recurrent and metastatic thyroid cancer of follicular cell origin. Between 30% and 40% of thyroid cancers are either resistant or become resistant to sadioactive iodine. Increased sodium-iodide symporter (NIS) and decreased Pendrin (PDS) activity may be associated with increased radioactive iodine effectiveness. In this investigation the effects of Trichostatin A (TSA), a histone deacetylating inhibitor, on human thyroid NIS and PDS gene expression was investigated. Method. Cell lines from papillary, Hürthle, and follicular cell carcinomas were treated with TSA for 72 hours at concentrations up to 100 ng/mL. NIS and PDS gene expression was determined using quantitative RT-polymerase chain reaction. Results. NIS messenger RNA expression in cell carcinomas was increased 107- (1.8-307) and 217- (5.7-408) fold in papillary, 39- (20-63) and 58- (37-80) fold in Hürthle, and 459- (178-810) and 781- (412-1229) fold in follicular after treatment with 50 and 100 ng/mL of TSA, respectively. PDS messenger RNA expression in cell carcinomas was decreased 0.22- (0.05-0.45) and 0.27- (0.09-0.47) fold in papillary, 0.53- (0.46-0.60) and 0.54- (0.44-0.64) fold in Hürthle, and 0.32- (0.26-0.39) and 0.56- (0.47-0.64) fold in follicular, after the same treatment. Conclusions. In thyroid cancer cell lines, TSA dramatically increased NIS gene expression and reduced PDS expression. The increased NIS expression and reduced PDS expression may make radioiodine therapy more effective in patients with thyroid cancer, especially when the tumors have no or low uptake of radioiodine.

AB - Background. Radioactive iodine is used to identify and treat recurrent and metastatic thyroid cancer of follicular cell origin. Between 30% and 40% of thyroid cancers are either resistant or become resistant to sadioactive iodine. Increased sodium-iodide symporter (NIS) and decreased Pendrin (PDS) activity may be associated with increased radioactive iodine effectiveness. In this investigation the effects of Trichostatin A (TSA), a histone deacetylating inhibitor, on human thyroid NIS and PDS gene expression was investigated. Method. Cell lines from papillary, Hürthle, and follicular cell carcinomas were treated with TSA for 72 hours at concentrations up to 100 ng/mL. NIS and PDS gene expression was determined using quantitative RT-polymerase chain reaction. Results. NIS messenger RNA expression in cell carcinomas was increased 107- (1.8-307) and 217- (5.7-408) fold in papillary, 39- (20-63) and 58- (37-80) fold in Hürthle, and 459- (178-810) and 781- (412-1229) fold in follicular after treatment with 50 and 100 ng/mL of TSA, respectively. PDS messenger RNA expression in cell carcinomas was decreased 0.22- (0.05-0.45) and 0.27- (0.09-0.47) fold in papillary, 0.53- (0.46-0.60) and 0.54- (0.44-0.64) fold in Hürthle, and 0.32- (0.26-0.39) and 0.56- (0.47-0.64) fold in follicular, after the same treatment. Conclusions. In thyroid cancer cell lines, TSA dramatically increased NIS gene expression and reduced PDS expression. The increased NIS expression and reduced PDS expression may make radioiodine therapy more effective in patients with thyroid cancer, especially when the tumors have no or low uptake of radioiodine.

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