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The AMPK-activator AICAR in thyroid cancer: effects on CXCL8 secretion and on CXCL8-induced neoplastic cell migration

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Abstract

Purpose

The AMPK-activator AICAR recently raised great interest for its anti-cancer properties. With specific regard to thyroid cancer, AICAR reduces cancer cell growth, invasion and metastasis. CXCL8, a chemokine with several recognized tumorigenic effects, is abundantly secreted in thyroid cancer microenvironment. The aim of this study was to investigate if AICAR could inhibit the basal and the TNFα-induced CXCL8 secretion in normal human thyroid cells (NHT) and in thyroid cancer cell lines TPC-1 and BCPAP (RET/PTC and BRAFV600e mutated, respectively).

Methods

The effect of AICAR on basal and CXCL8-induced cell migration was assessed. Cells were incubated with AICAR (0.05, 0.5, 1, 2 mM) alone or in combination with TNF-α (10 ng/ml) for 24 h. CXCL8 concentrations were measured in cell supernatants. Transwell migration assays were performed in NHT, TPC-1 and BCPAP, basally and after treatment with AICAR (2 mM) and rh-CXCL8 (50 ng/ml) alone or in combination.

Results

AICAR dose dependently inhibited the basal secretion of CXCL8 in TPC-1 (F = 4.26; p < 0.007) and BCPAP (F = 6.75; p < 0.0001) but not in NHT. TNFα-induced CXCL8 secretion was dose dependently reduced by AICAR in NHT (F = 9.99; p < 0.0001), TPC-1 (F = 9.25; p < 0.0001) and BCPAP (F = 6.82; p < 0.0001). AICAR significantly reduced the basal migration of TPC-1 and BCPAP but not of NHT.

Conclusions

CXCL8-induced cell migration was inhibited in NHT, TPC-1 and BCPAP. This is the first demonstration of the inhibition of CXCL8 secretion exerted by AICAR in TPC-1 and BCPAP indicating that the anti-cancer properties of AICAR are, at least in part, mediated by its ability to reduce the pro-tumorigenic effects of CXCL8.

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Author notes

  1. O. Awwad and F. Coperchini contributed equally to this study.

Authors and Affiliations

  1. Department of Biopharmaceutics and Clinical Pharmacy, The University of Jordan, Amman, 11937, Jordan

    O. Awwad

  2. Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, ICS Maugeri I.R.C.C.S, University of Pavia, Via S. Maugeri 10, 27100, Pavia, Italy

    F. Coperchini, S. Massara, L. Croce, L. Chiovato & M. Rotondi

  3. Allergy and Immunology Unit, ICS Maugeri I.R.C.C.S, 27100, Pavia, Italy

    P. Pignatti

  4. Molecular Cardiology, ICS-Maugeri, Via Maugeri 10/10°, 27100, Pavia, Italy

    M. Denegri

  5. Department of Molecular Medicine, University of Pavia, Pavia, Italy

    C. A. Di Buduo, V. Abbonante & A. Balduini

  6. Biotechnology Research Laboratories, IRCCS San Matteo Foundation, Pavia, Italy

    C. A. Di Buduo, V. Abbonante & A. Balduini

  7. Department of Biomedical Engineering, Tufts University, Medford, MA, USA

    A. Balduini

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  1. O. Awwad
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Correspondence to L. Chiovato.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Awwad, O., Coperchini, F., Pignatti, P. et al. The AMPK-activator AICAR in thyroid cancer: effects on CXCL8 secretion and on CXCL8-induced neoplastic cell migration. J Endocrinol Invest 41, 1275–1282 (2018). https://doi.org/10.1007/s40618-018-0862-8

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