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SHR Neuro Krebs Kardio Lipid

Fröhlich, E; Czarnocka, B; Brossart, P; Wahl, R.
Antitumor effects of arsenic trioxide in transformed human thyroid cells.
Thyroid. 2008; 18(11):1183-1193
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Autor/innen der Med Uni Graz:
Fröhlich Eleonore
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Abstract:
BACKGROUND: To improve radioiodine treatment of metastasized differentiated thyroid carcinomas, substances that increase iodide uptake are needed. Many tumors are not responsive to retinoic acid as a differentiating agent. Therefore, identification of other differentiating substances is needed. Arsenic trioxide (ATO) was investigated for its potential to increase iodide uptake. METHODS: The action of ATO on proliferation, differentiation, and apoptosis was evaluated in follicular and papillary thyroid carcinoma cell lines. To get insight into the mode of action of ATO, coincubations with inhibitors of the phosphoinositide 3 (PI3) kinase pathway (V-Akt Murine Thymoma Viral Oncogene Homolog 1, Akt inhibitors) were performed; glutathione (GSH) levels were determined, as well as synergistic effects of ATO with inhibitors of GSH metabolism, inductors of oxidative stress. As a potential additional target of the pleiotropic action of ATO, its effect on glucose uptake was investigated. The expression of sodium iodide symporter, pendrin, phospho-Akt, and glucose transporter 1 was studied to reveal a potential effect of ATO on the transcription of specific genes. RESULTS: ATO reduced proliferation, increased iodide uptake and apoptosis, and, as an additional new mechanism, decreased glucose uptake in transformed thyrocytes. The pharmacological reduction of the amount of reduced GSH was effective in enhancing the differentiating action of ATO, whereas the combination of ATO with Akt-1 inhibitors reduced cell number but did not increase differentiation. CONCLUSIONS: Our study suggests a new therapeutic option for postoperative treatment of radioiodine nonresponsive differentiated thyroid carcinomas.
Find related publications in this database (using NLM MeSH Indexing)
1-Phosphatidylinositol 3-Kinase - metabolism
Adenocarcinoma, Follicular - drug therapy
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Arsenicals - pharmacology
Biological Transport, Active - drug effects
Carcinoma, Papillary - drug therapy
Cell Differentiation - drug effects
Cell Line, Tumor -
Cell Proliferation - drug effects
Cell Transformation, Neoplastic - drug effects
Glucose - metabolism
Glutathione - metabolism
Humans -
Iodides - metabolism
Iodine Radioisotopes - therapeutic use
Oncogene Protein v-akt - antagonists and inhibitors
Oxides - pharmacology
Radiation Tolerance -
Reactive Oxygen Species - metabolism
Thyroid Neoplasms - drug therapy

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