title: Effects of BP-14, a novel cyclin-dependent kinase inhibitor, on anaplastic thyroid cancer cells.
abstract: Anaplastic thyroid carcinoma (ATC) is an extremely aggressive human malignancy characterized by a marked degree of invasiveness, absense of features of thyroid differentiation and resistance to current medical treatment. It is well known that ATCs are characterized by deregulation of genes related to cell cycle regulation, i.e., cyclin-dependent kinases (CDKs) and endogenous cyclin-dependent kinase inhibitors (CDKIs). Therefore, in the present study, the effect of a novel exogenous cyclin-dependent kinase inhibitor, BP-14, was investigated in three human ATC cell lines. The ATC-derived cell lines FRO, SW1736 and 8505C were treated with BP-14 alone or in combination with the mTOR inhibitor everolimus. In all ATC cell lines, treatment with BP-14 decreased cell viability and, in two of them, BP-14 modified expression of genes involved in epithelial-mesenchymal transition. Thus, our data indicate that BP-14 is a potential new compound effective against ATC. Combined treatment with BP-14 and the mTOR inhibitor everolimus had a strong synergistic effect on cell viability in all three cell lines, suggesting that the combined used of CDK and mTOR inhibitors may be a useful strategy for ATC treatment.
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Allegri
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Baldan
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Mio
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Puppin
authors.affiliation: Department of Health Sciences, University 'Magna Graecia' of Catanzaro, Catanzaro, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.affiliation: Laboratory of Growth Regulators, Center of the Region Haná for Biotechnological and Agricultural Research, Palacký University and Institute of Experimental Botany AS CR, CZ-77111 Olomuc, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kryštof
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D000068338:Everolimus / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000235:genetics*
chemical_list: C588398:N2-(4-aminocyclohexyl)-9-cyclopentyl-N6-((6-(2-furyl)-3-pyridyl)methyl)purine-2,6-diamine; D047428:Protein Kinase Inhibitors; D015075:2-Aminopurine; D000068338:Everolimus