Iodine-131 induces apoptosis in HTori-3 human thyrocyte cell line and G2/M phase arrest in a p53-independent pathway

Abstract

Iodine-131 is known to destroy residual thyroid tissue following surgical resection of differentiated thyroid carcinoma and is widely used to treat hyperthyroidism. However, the mechanism by which iodine-131 induces apoptosis and cell cycle arrest in the human thyrocyte cell line, Htori-3, remains to be elucidated. In the present study, the cytotoxic effect of iodine-131 on the HTori-3 cell line and the underlying mechanism of iodine-131-induced cell apoptosis were investigated. Cell viability was analyzed using an MTT assay, while cell apoptosis and cell cycle arrest were determined using flow cytometry. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were performed to determine the changes in the expression levels of p53, B-cell lymphoma 2 (Bcl-2), Fas and growth arrest and DNA damage-inducible 45 (GADD45), following iodine-131 treatment. The results demonstrated that iodine-131 may inhibit HTori-3 cell growth via cell apoptosis and G2/M phase arrest in a time- and dose-dependent manner. The iodine-131 dose required for 50% growth inhibition of HTori-3 cell viability 48 h after treatment was 27.75±2.22 MBq/ml. Upregulation of Fas and downregulation of Bcl-2 expression levels were observed following iodine-131 treatment. The results of RT-qPCR revealed an increase in the GADD45 mRNA expression following HTori-3 cell exposure to iodine-131. Notably, the mRNA and protein expression levels of p53 were not altered following iodine-131 treatment. In conclusion, iodine-131 may induce apoptosis in HTori-3 cells by downregulating the expression of Bcl-2 and upregulating the expression of Fas. In addition, iodine-131 may upregulate GADD45 mRNA expression in HTori-3 cells, resulting in G2/M phase arrest in a p53-independent pathway.