This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vitale, M. Articles by Rossi, G. Search for Related Content PubMed PubMed Citation Articles by Vitale, M. Articles by Rossi, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CYCLOHEXIMIDE POTASSIUM IODIDE PROPYL THIOURACIL

Iodide Excess Induces Apoptosis in Thyroid Cells through a p53-Independent Mechanism Involving Oxidative Stress¹

Dipartimento di Biologia e Patologia Cellulare e Molecolare (M.V., T.D., G.R.), Università Federico II, Naples 80131, Italy; Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica (F.D., GF.F.), Università Federico II, Naples, Italy; Centro di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" (S.S., G.R.), C.N.R.; Dipartimento di Endocrinologia (F.B., E.M.), Università di Pisa, 56100 Pisa, Italy

Address all correspondence and requests for reprints to: Mario Vitale, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Via S. Pansini, 5 Napoli, 80131, Italy. E-mail: mavitale{at}unina.it

Thyroid toxicity of iodide excess has been demonstrated in animals fed with an iodide-rich diet; in vitro iodide is cytotoxic, inhibits cell growth, and induces morphological changes in thyroid cells of some species. In this study, we investigated the effect of iodide excess in an immortalized thyroid cell line (TAD-2) in primary cultures of human thyroid cells and in cells of nonthyroid origin. Iodide displayed a dose-dependent cytotoxicity in both TAD-2 and primary thyroid cells, although at different concentrations, whereas it had no effect on cells of nonthyroid origin. Thyroid cells treated with iodide excess underwent apoptosis, as evidenced by morphological changes, plasma membrane phosphatidylserine exposure, and DNA fragmentation. Apoptosis was unaffected by protein synthesis inhibition, whereas inhibition of peroxidase enzymatic activity by propylthiouracil completely blocked iodide cytotoxicity. During KI treatment, reactive oxygen species were produced, and lipid peroxide levels increased markedly. Inhibition of endogenous p53 activity did not affect the sensitivity of TAD-2 cells to iodide, and Western blot analysis demonstrated that p53, Bcl-2, Bcl-XL, and Bax protein expression did not change when cells were treated with iodide. These data indicate that excess molecular iodide, generated by oxidation of ionic iodine by endogenous peroxidases, induces apoptosis in thyroid cells through a mechanism involving generation of free radicals. This type of apoptosis is p53 independent, does not require protein synthesis, and is not induced by modulation of Bcl-2, Bcl-XL, or Bax protein expression.

This article has been cited by other articles:

				O Arroyo-Helguera, E Rojas, G Delgado, and C Aceves Signaling pathways involved in the antiproliferative effect of molecular iodine in normal and tumoral breast cells: evidence that 6-iodolactone mediates apoptotic effects Endocr. Relat. Cancer, December 1, 2008; 15(4): 1003 - 1011. [Abstract] [Full Text] [PDF]

				H. Li, K. Richard, B. McKinnon, and R. H. Mortimer Effect of Iodide on Human Choriogonadotropin, Sodium-Iodide Symporter Expression, and Iodide Uptake in BeWo Choriocarcinoma Cells J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 4046 - 4051. [Abstract] [Full Text] [PDF]

				O Arroyo-Helguera, B Anguiano, G Delgado, and C Aceves Uptake and antiproliferative effect of molecular iodine in the MCF-7 breast cancer cell line Endocr. Relat. Cancer, December 1, 2006; 13(4): 1147 - 1158. [Abstract] [Full Text] [PDF]

				A. Shrivastava, M. Tiwari, R. A. Sinha, A. Kumar, A. K. Balapure, V. K. Bajpai, R. Sharma, K. Mitra, A. Tandon, and M. M. Godbole Molecular Iodine Induces Caspase-independent Apoptosis in Human Breast Carcinoma Cells Involving the Mitochondria-mediated Pathway J. Biol. Chem., July 14, 2006; 281(28): 19762 - 19771. [Abstract] [Full Text] [PDF]

				F Al-Khafaji, M Wiltshire, D Fuhrer, G Mazziotti, M D Lewis, P J Smith, and M Ludgate Biological activity of activating thyrotrophin receptor mutants: modulation by iodide J. Mol. Endocrinol., February 1, 2005; 34(1): 209 - 220. [Abstract] [Full Text] [PDF]

				L. Zhang, S. Sharma, L. X. Zhu, T. Kogai, J. M. Hershman, G. A. Brent, S. M. Dubinett, and M. Huang Nonradioactive Iodide Effectively Induces Apoptosis in Genetically Modified Lung Cancer Cells Cancer Res., August 15, 2003; 63(16): 5065 - 5072. [Abstract] [Full Text] [PDF]

				N F Fanning, B J Manning, J Buckley, and H P Redmond Iodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway Br. J. Radiol., November 1, 2002; 75(899): 861 - 873. [Abstract] [Full Text] [PDF]

				E. Martino, L. Bartalena, F. Bogazzi, and L. E. Braverman The Effects of Amiodarone on the Thyroid Endocr. Rev., April 1, 2001; 22(2): 240 - 254. [Abstract] [Full Text]

				T. Di Matola, F. D’Ascoli, G. Fenzi, G. Rossi, E. Martino, F. Bogazzi, and M. Vitale Amiodarone Induces Cytochrome c Release and Apoptosis through an Iodine-Independent Mechanism J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4323 - 4330. [Abstract] [Full Text]