title: 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.
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Weixiao
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gao
authors.affiliation: Department of Public Health, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Guo
authors.affiliation: Endocrinology Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hou
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Mingqi
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D059447:Cell Cycle Checkpoints / Q000528:radiation effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007457:Iodine Radioisotopes; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D013961:Thyroid Gland / Q000166:cytology* / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000097642:GADD45 Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007457:Iodine Radioisotopes; D053218:Receptors, Death Domain; D016159:Tumor Suppressor Protein p53; D000097642:GADD45 Proteins