title: Mechanisms of apoptosis in irradiated and sunitinib-treated follicular thyroid cancer cells.
abstract: The multikinase inhibitor sunitinib (S) seems to have promising potential in the treatment of thyroid cancer. We focused on the impact of S and/or irradiation (R) on mechanisms of apoptosis in follicular thyroid cancer cells. The effects of R, S and their combination were evaluated 2 and 4 days after treatment, using the human thyroid cancer cell line CGTH W-1. The transcription of genes involved in the regulation of apoptosis was investigated using quantitative real-time PCR. Western blot analyses of caspases and survivin were also performed. S elevated BAX (day 4), CASP9, CASP3, BIRC5 (day 4) and PRKACA (day 4) gene expression, whereas the mRNAs of BCL2, CASP8, PRKCA, ERK1, and ERK2 were not significantly changed. S, R and R+S clearly induced caspase-9 protein and elevated caspase-3 activity. Survivin was down-regulated at day 4 in control cells and the expression was blunted by S treatment. R+S induced survivin expression at day 2 followed by a reduction at day 4 of treatment. Sunitinib and the combined application with radiation induced apoptosis in follicular thyroid cancer cells via the intrinsic pathway of apoptosis. In addition, sunitinib might induce apoptosis via decreased expression of the anti-apoptotic protein survivin. These findings suggest the potential use of sunitinib for the treatment of poorly differentiated follicular thyroid carcinomas.
authors.affiliation: Department of Nuclear Medicine, University of Regensburg, Regensburg, Germany.
authors.forename: Jirka
authors.initials: J
authors.lastname: Grosse
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Warnke
authors.forename: Markus
authors.initials: M
authors.lastname: Wehland
authors.forename: Jessica
authors.initials: J
authors.lastname: Pietsch
authors.forename: Fabian
authors.initials: F
authors.lastname: Pohl
authors.forename: Petra
authors.initials: P
authors.lastname: Wise
authors.forename: Nils E
authors.initials: NE
authors.lastname: Magnusson
authors.forename: Christoph
authors.initials: C
authors.lastname: Eilles
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000473:pathology* / Q000628:therapy; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D000077210:Sunitinib; D000077022:Survivin; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000628:therapy
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D007211:Indoles; D051034:Inhibitor of Apoptosis Proteins; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077022:Survivin; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases; D000077210:Sunitinib