Cl-IB-MECA inhibits human thyroid cancer cell proliferation independently of A3 adenosine receptor activation

Silvana Morello, Antonello Petrella, Michela Festa, Ada Popolo, Mario Monaco, Emilia Vuttariello, Gennaro Chiappetta, Luca Parente, Aldo Pinto

Research output: Contribution to journalArticle

Abstract

A3 adenosine receptor (A3AR) agonists have been reported to modulate cellular proliferation. This work was aimed to investigate the expression and the possible implication of A3AR in the human thyroid carcinomas. Normal thyroid tissue samples did not express A3 adenosine receptor, while primary thyroid cancer tissues expressed high level of A3AR, as determined by immunohistochemistry analysis. In human papillary thyroid carcinoma cell line, NPA, at concentrations ≥10 ?M, the A3AR-selective agonist 2-chloro-N 6-(3-iodobenzyl)adenosine-5′-N-methylcarboxamide (Cl-IB-MECA) produced inhibition of cell growth, by blocking the G1 cell cycle phase in a concentration- and time-dependent manner. This effect was well correlated with a reduction of protein expression of cyclins D1 and E2 after 24 hours of Cl-IB-MECA treatment. Moreover Cl-IB-MECA induced dephosphorylation of ERK1/2 in a time- and concentration-dependent manner, which in turn inhibits cell proliferation. The effect of Cl-IB-MECA was not prevented by A3AR antagonists, MRS1191 or MRS1523 or FA385. Furthermore, neither nucleoside transporter inhibitors, Dypiridamole and NBTI, nor the A1, A2A and A2B receptors antagonists were able to block the response to Cl-IB-MECA. Although Cl-IB-MECA has been shown to influence cell death and survival in other systems through an A3AR-mediated mechanism, in NPA cells the growth inhibition induced by micromolar concentrations of Cl-IB-MECA is not related to A3AR activation and hence that its effects on human papillary carcinoma cell line seem to be independent of the presence of this receptor subtype.

Original languageEnglish
Pages (from-to)278-284
Number of pages7
JournalCancer Biology and Therapy
Volume7
Issue number2
Publication statusPublished - Feb 2008

Keywords

  • A3 adenosine receptor
  • Adenosine receptor antagonist
  • cell cycle arrest
  • Cl-IB-MECA
  • NPA
  • Thyroid cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Morello, S., Petrella, A., Festa, M., Popolo, A., Monaco, M., Vuttariello, E., Chiappetta, G., Parente, L., & Pinto, A. (2008). Cl-IB-MECA inhibits human thyroid cancer cell proliferation independently of A3 adenosine receptor activation. Cancer Biology and Therapy, 7(2), 278-284.