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

Joanna Klubo-Gwiezdzinska; John Costello Jr; Kirk Jensen; Aneeta Patel; Rok Tkavc; Douglas Van Nostrand; Kenneth D Burman; Leonard Wartofsky; Vasyl Vasko

doi:10.1530/EC-17-0138

Endocrine Connections (Sep 2017)

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

Joanna Klubo-Gwiezdzinska,
John Costello Jr,
Kirk Jensen,
Aneeta Patel,
Rok Tkavc,
Douglas Van Nostrand,
Kenneth D Burman,
Leonard Wartofsky,
Vasyl Vasko

Affiliations

Joanna Klubo-Gwiezdzinska: National 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, USA
John Costello Jr: Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Kirk Jensen: Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Aneeta Patel: Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Rok Tkavc: Department of Pathology, Uniformed Services University of the Health Sciences, Henry Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA
Douglas Van Nostrand: Division of Endocrinology, Department of Medicine, Medstar Washington Hospital Center, Washington Hospital Center, Northwest, Washington, District of Columbia, USA
Kenneth D Burman: Division of Endocrinology, Department of Medicine, Medstar Washington Hospital Center, Washington Hospital Center, Northwest, Washington, District of Columbia, USA
Leonard Wartofsky: Division of Endocrinology, Department of Medicine, Medstar Washington Hospital Center, Washington Hospital Center, Northwest, Washington, District of Columbia, USA
Vasyl Vasko: Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

DOI: https://doi.org/10.1530/EC-17-0138
Journal volume & issue: Vol. 6, no. 7
pp. 469 – 478

Abstract

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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.

Published in Endocrine Connections

ISSN: 2049-3614 (Online)
Publisher: Bioscientifica
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the endocrine glands. Clinical endocrinology
Website: http://www.endocrineconnections.com/

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