Amifostine does not protect thyroid cancer cells in DNA damaging in vitro models

Background: Amifostine is a potent scavenger of reactive oxygen species that is used for the salivary gland protection during therapy with radioactive iodine for thyroid cancer. There are no data on the potential effect of amifostine on thyroid cancer cells. Methods: We investigated the effects of...

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Main Authors: Joanna Klubo-Gwiezdzinska, John Costello Jr, Kirk Jensen, Aneeta Patel, Rok Tkavc, Douglas Van Nostrand, Kenneth D Burman, Leonard Wartofsky, Vasyl Vasko
Format: Article
Language:English
Published: Bioscientifica 2017-09-01
Series:Endocrine Connections
Subjects:
Online Access:http://www.endocrineconnections.com/content/6/7/469.full
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author Joanna Klubo-Gwiezdzinska
John Costello Jr
Kirk Jensen
Aneeta Patel
Rok Tkavc
Douglas Van Nostrand
Kenneth D Burman
Leonard Wartofsky
Vasyl Vasko
author_facet Joanna Klubo-Gwiezdzinska
John Costello Jr
Kirk Jensen
Aneeta Patel
Rok Tkavc
Douglas Van Nostrand
Kenneth D Burman
Leonard Wartofsky
Vasyl Vasko
author_sort Joanna Klubo-Gwiezdzinska
collection DOAJ
description Background: Amifostine is a potent scavenger of reactive oxygen species that is used for the salivary gland protection during therapy with radioactive iodine for thyroid cancer. There are no data on the potential effect of amifostine on thyroid cancer cells. Methods: We investigated the effects of the active form of amifostine (WR-1065) on the response of thyroid cancer cells to treatment with DNA-damaging agents. WR-1065 was examined in human thyroid cancer cell lines (FTC133, TPC1, BCPAP and C643) and embryonic fibroblast cells NIH3T3. DNA damage was induced by exposure to H2O2 (0.1 mM), by treatment with the radiomimetic neocarzinostatin (NCS 250 ng/mL) and by γ-radiation (6 Gy). DNA damage, cell viability and apoptosis were examined. Results: We demonstrated the selective action of WR-1065 (0.1 mM), which prevented oxidative stress–induced DNA damage in fibroblasts, but did not protect thyroid cancer cells from DNA damage and apoptosis documented by caspase-3 and PARP cleavage after exposure to H2O2, NCS and γ-radiation. Prolonged exposure to WR-1065 (0.1 mM for 24 h) was toxic for thyroid cancer cells; this treatment decreased the number of viable cells by 8% in C643 cells, 47% in TPC cells, 92% in BCPAP cells and 82% in FTC 133 cells. The cytotoxic effects of WR-1065 were not associated with induction of apoptosis. Conclusions: Our data show that amifostine has no protective effect on thyroid cancer cells against DNA-damaging agents in vitro and suggest that amifostine will not attenuate the efficacy of radioiodine treatment in patients with thyroid cancer.
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spelling doaj.art-19b9866d1f2a490a850174fada7c7fb82022-12-22T03:37:32ZengBioscientificaEndocrine Connections2049-36142049-36142017-09-016746947810.1530/EC-17-0138Amifostine does not protect thyroid cancer cells in DNA damaging in vitro modelsJoanna Klubo-Gwiezdzinska0John Costello Jr1Kirk Jensen2Aneeta Patel3Rok Tkavc4Douglas Van Nostrand5Kenneth D Burman6Leonard Wartofsky7Vasyl Vasko8National Institute of Health, NIDDK, Office 10 Center Drive, Bethesda, Maryland, USA; Division of Endocrinology, Department of Medicine, Medstar Washington Hospital Center, Washington Hospital Center, Northwest, Washington, District of Columbia, USADepartment of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USADepartment of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USADepartment of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USADepartment of Pathology, Uniformed Services University of the Health Sciences, Henry Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USADivision of Endocrinology, Department of Medicine, Medstar Washington Hospital Center, Washington Hospital Center, Northwest, Washington, District of Columbia, USADivision of Endocrinology, Department of Medicine, Medstar Washington Hospital Center, Washington Hospital Center, Northwest, Washington, District of Columbia, USADivision of Endocrinology, Department of Medicine, Medstar Washington Hospital Center, Washington Hospital Center, Northwest, Washington, District of Columbia, USADepartment of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USABackground: Amifostine is a potent scavenger of reactive oxygen species that is used for the salivary gland protection during therapy with radioactive iodine for thyroid cancer. There are no data on the potential effect of amifostine on thyroid cancer cells. Methods: We investigated the effects of the active form of amifostine (WR-1065) on the response of thyroid cancer cells to treatment with DNA-damaging agents. WR-1065 was examined in human thyroid cancer cell lines (FTC133, TPC1, BCPAP and C643) and embryonic fibroblast cells NIH3T3. DNA damage was induced by exposure to H2O2 (0.1 mM), by treatment with the radiomimetic neocarzinostatin (NCS 250 ng/mL) and by γ-radiation (6 Gy). DNA damage, cell viability and apoptosis were examined. Results: We demonstrated the selective action of WR-1065 (0.1 mM), which prevented oxidative stress–induced DNA damage in fibroblasts, but did not protect thyroid cancer cells from DNA damage and apoptosis documented by caspase-3 and PARP cleavage after exposure to H2O2, NCS and γ-radiation. Prolonged exposure to WR-1065 (0.1 mM for 24 h) was toxic for thyroid cancer cells; this treatment decreased the number of viable cells by 8% in C643 cells, 47% in TPC cells, 92% in BCPAP cells and 82% in FTC 133 cells. The cytotoxic effects of WR-1065 were not associated with induction of apoptosis. Conclusions: Our data show that amifostine has no protective effect on thyroid cancer cells against DNA-damaging agents in vitro and suggest that amifostine will not attenuate the efficacy of radioiodine treatment in patients with thyroid cancer.http://www.endocrineconnections.com/content/6/7/469.fullthyroid canceramifostineradiationDNA damage
spellingShingle Joanna Klubo-Gwiezdzinska
John Costello Jr
Kirk Jensen
Aneeta Patel
Rok Tkavc
Douglas Van Nostrand
Kenneth D Burman
Leonard Wartofsky
Vasyl Vasko
Amifostine does not protect thyroid cancer cells in DNA damaging in vitro models
Endocrine Connections
thyroid cancer
amifostine
radiation
DNA damage
title Amifostine does not protect thyroid cancer cells in DNA damaging in vitro models
title_full Amifostine does not protect thyroid cancer cells in DNA damaging in vitro models
title_fullStr Amifostine does not protect thyroid cancer cells in DNA damaging in vitro models
title_full_unstemmed Amifostine does not protect thyroid cancer cells in DNA damaging in vitro models
title_short Amifostine does not protect thyroid cancer cells in DNA damaging in vitro models
title_sort amifostine does not protect thyroid cancer cells in dna damaging in vitro models
topic thyroid cancer
amifostine
radiation
DNA damage
url http://www.endocrineconnections.com/content/6/7/469.full
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