8-Cl-cAMP and PKA I-selective cAMP analogs effectively inhibit undifferentiated thyroid cancer cell growth

• Published in: Endocrine 2017-05, Vol.56 (2), p.388-398
• Main Authors: Grassi, Elisa Stellaria, Dicitore, Alessandra, Negri, Irene, Borghi, Maria Orietta, Vitale, Giovanni, Persani, Luca
• Format: Article
• Language: English
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives; 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Adenosine; Adenosine kinase; Apoptosis; Apoptosis - drug effects; Cell activation; Cell Cycle - drug effects; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - pathology; Cyclic AMP; Cyclic AMP - analogs & derivatives; Cyclic AMP - pharmacology; Diabetes; Endocrinology; Humanities and Social Sciences; Humans; Internal Medicine; Intracellular; Kinases; Medicine; Medicine & Public Health; multidisciplinary; Original Article; Phosphorylation - drug effects; Protein kinase A; Proteins; Science; Signal Transduction - drug effects; Taste; Thyroid cancer; Thyroid Gland - drug effects; Thyroid Gland - pathology; Thyroid Neoplasms - pathology; Tumor cell lines; Western blotting
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-016-1057-8

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.