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

O Awwad1, F Coperchini2, P Pignatti3

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

Journal of Endocrinological Investigation
|March 17, 2018
PubMed
Abstract

Insights

AICAR significantly reduced CXCL8 secretion and cell migration in thyroid cancer cells. This suggests AICAR’s anti-cancer effects are partly due to its ability to inhibit pro-tumorigenic chemokine CXCL8.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • AMPK-activator AICAR exhibits anti-cancer properties, reducing growth, invasion, and metastasis in thyroid cancer.
  • CXCL8, a chemokine, is highly secreted in the thyroid cancer microenvironment and promotes tumorigenesis.

Purpose of the Study:

  • To investigate AICAR's effect on basal and TNFα-induced CXCL8 secretion in normal human thyroid (NHT) and thyroid cancer cell lines (TPC-1, BCPAP).
  • To assess AICAR's impact on cell migration in NHT, TPC-1, and BCPAP cells.

Main Methods:

  • Cells were treated with varying concentrations of AICAR alone or with TNF-α.
  • CXCL8 concentrations in cell supernatants were measured.
  • Transwell migration assays were performed to evaluate cell migration.

Main Results:

  • AICAR dose-dependently inhibited basal CXCL8 secretion in TPC-1 and BCPAP cells.
  • AICAR reduced TNFα-induced CXCL8 secretion in NHT, TPC-1, and BCPAP cells.
  • AICAR significantly inhibited basal cell migration in TPC-1 and BCPAP cells.

Conclusions:

  • AICAR inhibits both basal and TNFα-induced CXCL8 secretion in thyroid cancer cell lines.
  • AICAR reduces cell migration in normal and cancerous thyroid cells.
  • AICAR's anti-cancer effects in thyroid cancer are partly mediated by reducing CXCL8's pro-tumorigenic activity.
Keywords:
AICARCXCL8ChemokinesMigrationThyroid cancer

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