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

O Awwad, F Coperchini, P Pignatti, M Denegri, S Massara, L Croce, C A Di Buduo, V Abbonante, A Balduini, L Chiovato, M Rotondi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1275-1282
Number of pages8
JournalJournal of Endocrinological Investigation
Volume41
Issue number11
DOIs
Publication statusPublished - Nov 2018

Keywords

  • Aminoimidazole Carboxamide/analogs & derivatives
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Humans
  • Interleukin-8/metabolism
  • Ribonucleotides/pharmacology
  • Thyroid Gland/pathology
  • Thyroid Neoplasms/metabolism
  • Tumor Necrosis Factor-alpha/pharmacology

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