title: 8-Cl-cAMP and PKA I-selective cAMP analogs effectively inhibit undifferentiated thyroid cancer cell growth.
abstract: The main purpose of our work was to evaluate the effects of different cyclic adenosine monophosphate analogs on thyroid cancer-derived cell lines. In particular we studied 8-chloroadenosine-3',5'-cyclic monophosphate, the most powerful cyclic adenosine monophosphate analog, and the protein kinase A I-selective combination of 8-hexylaminoadenosine-3',5'cyclic monophosphate and 8-piperidinoadenosine-3',5'-cyclic monophosphate. The cyclic adenosine monophosphate/protein kinase A pathway plays a fundamental role in the regulation of thyroid cells growth. Site-selective cyclic adenosine monophosphate analogs are a class of cyclic adenosine monophosphate-derivate molecules that has been synthesized to modulate protein kinase A activity. Although the cyclic adenosine monophosphate/protein kinase A pathway plays a fundamental role in the regulation of thyroid cells proliferation, there are currently no studies exploring the role of cyclic adenosine monophosphate analogs in thyroid cancer. We evaluated the effects on cell proliferation, apoptosis activation and alterations of different intracellular pathways using 3-(4,5-dimetylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytofluorimetry, western blotting, and kinase inhibitors. Our results show that both compounds have antiproliferative potential. Both treatments were able to modify protein kinase A RI/RII ratio, thus negatively influencing cancer cells growth. Moreover, the two treatments differentially modulated various signaling pathways that regulate cell proliferation and apoptosis. Both treatments demonstrated interesting characteristics that prompt further studies aiming to understand the intimate interaction between different intracellular pathways and possibly develop novel anticancer therapies for undifferentiated thyroid cancer.
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.
authors.forename: Elisa Stellaria
authors.initials: ES
authors.lastname: Grassi
authors.affiliation: Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Via Zucchi 18, Cusano Milanino, 20095, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dicitore
authors.affiliation: Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Via Zucchi 18, Cusano Milanino, 20095, Milan, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Negri
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.
authors.forename: Maria Orietta
authors.initials: MO
authors.lastname: Borghi
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.|Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Via Zucchi 18, Cusano Milanino, 20095, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy. luca.persani@unimi.it.|Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Via Zucchi 18, Cusano Milanino, 20095, Milan, Italy. luca.persani@unimi.it.|Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy. luca.persani@unimi.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013961:Thyroid Gland / Q000187:drug effects* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000473:pathology*
chemical_list: C000611750:8-hexylaminoadenosine-3',5'-cyclic monophosphate; C000611751:8-piperidinoadenosine-3',5'-cyclic monophosphate; D015124:8-Bromo Cyclic Adenosine Monophosphate; C044258:8-chloro-cyclic adenosine monophosphate; D000242:Cyclic AMP
keywords: Protein kinase A; Thyroid cancer; cAMP analogs