title: Rosuvastatin induces apoptosis in cultured human papillary thyroid cancer cells.
abstract: Statins show antiproliferative activity in various cancer cells. The aim of this study was to evaluate the effects of rosuvastatin treatment on papillary thyroid carcinoma. The papillary thyroid carcinoma (B-CPAP) and normal (Nthy-ori 3-1) thyroid cell lines were treated with rosuvastatin at 12.5, 18.5, 25, 50, 100, and 200 μM concentrations. After 48 and 72 h of rosuvastatin treatment, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, Ki-67 immunolabeling, FACS analysis, electron microscopy, caspase-3, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) analysis were performed. Decreased cell viability and G1 phase arrest were detected in papillary thyroid cell line treated with rosuvastatin. Positive immunoreactivity of Ki-67 and dose-dependent increase in S phase on Nthy-ori 3-1 cells were also detected. B-CPAP cells showed intense vacuolisation and autophagosomes with low concentrations and 48 h incubations, while Nthy-ori 3-1 cells showed these changes at higher concentrations. A decrease in the percentage of cells showing autophagy was determined with increasing concentrations of rosuvastatin in B-CPAP cells. Rosuvastatin treatment also caused a dose- and time-dependent increase in caspase-3 activity and apoptotic index by TUNEL assay in B-CPAP cells compared with the Nthy-ori 3-1 cells. Apoptotic cells with nuclear condensation and fragmentation were observed in B-CPAP cell line. Rosuvastatin induced autophagic changes in B-CPAP papillary thyroid cancer cells in lower doses and caused a shift from autophagy to apoptosis. Rosuvastatin may be an alternative treatment for refractory papillary thyroid cancer. Further in vivo studies are necessary to clarify the effects of rosuvastatin in papillary thyroid carcinoma and the clinical implications of rosuvastatin treatment.
authors.affiliation: Departments of Histology and Embryology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara 06100, Turkey. dilaraz@hacettepe.edu.tr
authors.forename: N Dilara
authors.initials: ND
authors.lastname: Zeybek
authors.forename: Nese Ersoz
authors.initials: NE
authors.lastname: Gulcelik
authors.forename: F Figen
authors.initials: FF
authors.lastname: Kaymaz
authors.forename: Can
authors.initials: C
authors.lastname: Sarisozen
authors.forename: Imran
authors.initials: I
authors.lastname: Vural
authors.forename: Ebru
authors.initials: E
authors.lastname: Bodur
authors.forename: Hande
authors.initials: H
authors.lastname: Canpinar
authors.forename: Aydan
authors.initials: A
authors.lastname: Usman
authors.forename: Esin
authors.initials: E
authors.lastname: Asan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005464:Fluorobenzenes / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009994:Osmolar Concentration; D010282:Parathyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors; D014617:Vacuoles / Q000187:drug effects / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019394:Ki-67 Antigen; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; C505407:CASP3 protein, human; D053148:Caspase 3