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

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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.

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Authors and Affiliations

  1. Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy

    Elisa Stellaria Grassi, Maria Orietta Borghi, Giovanni Vitale & Luca Persani

  2. Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Via Zucchi 18, Cusano Milanino, 20095, Milan, Italy

    Alessandra Dicitore, Irene Negri, Giovanni Vitale & Luca Persani

  3. Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

    Luca Persani

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  1. Elisa Stellaria Grassi
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  2. Alessandra Dicitore
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  3. Irene Negri
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  4. Maria Orietta Borghi
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Correspondence to Luca Persani.

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Negri’s present address: IRIBHM, Institute of Interdisciplinary Research in Molecular Human Biology, Université Libre de Bruxelles, Brussels, Belgium

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Grassi, E.S., Dicitore, A., Negri, I. et al. 8-Cl-cAMP and PKA I-selective cAMP analogs effectively inhibit undifferentiated thyroid cancer cell growth. Endocrine 56, 388–398 (2017). https://doi.org/10.1007/s12020-016-1057-8

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