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

Fingerprint

AMP-Activated Protein Kinases
Thyroid Neoplasms
Cell Movement
Thyroid Gland
AICA ribonucleotide
Neoplasms
Factor IX
Tumor Microenvironment
Interleukin-8
Neoplasm Metastasis

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

Cite this

The AMPK-activator AICAR in thyroid cancer : effects on CXCL8 secretion and on CXCL8-induced neoplastic cell migration. / Awwad, O; Coperchini, F; Pignatti, P; Denegri, M; Massara, S; Croce, L; Di Buduo, C A; Abbonante, V; Balduini, A; Chiovato, L; Rotondi, M.

In: Journal of Endocrinological Investigation, Vol. 41, No. 11, 11.2018, p. 1275-1282.

Research output: Contribution to journalArticle

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title = "The AMPK-activator AICAR in thyroid cancer: effects on CXCL8 secretion and on CXCL8-induced neoplastic cell migration",
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.",
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",
author = "O Awwad and F Coperchini and P Pignatti and M Denegri and S Massara and L Croce and {Di Buduo}, {C A} and V Abbonante and A Balduini and L Chiovato and M Rotondi",
year = "2018",
month = "11",
doi = "10.1007/s40618-018-0862-8",
language = "English",
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pages = "1275--1282",
journal = "Journal of Endocrinological Investigation",
issn = "0391-4097",
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TY - JOUR

T1 - The AMPK-activator AICAR in thyroid cancer

T2 - effects on CXCL8 secretion and on CXCL8-induced neoplastic cell migration

AU - Awwad, O

AU - Coperchini, F

AU - Pignatti, P

AU - Denegri, M

AU - Massara, S

AU - Croce, L

AU - Di Buduo, C A

AU - Abbonante, V

AU - Balduini, A

AU - Chiovato, L

AU - Rotondi, M

PY - 2018/11

Y1 - 2018/11

N2 - 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.

AB - 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.

KW - Aminoimidazole Carboxamide/analogs & derivatives

KW - Cell Line, Tumor

KW - Cell Movement/drug effects

KW - Cell Proliferation/drug effects

KW - Humans

KW - Interleukin-8/metabolism

KW - Ribonucleotides/pharmacology

KW - Thyroid Gland/pathology

KW - Thyroid Neoplasms/metabolism

KW - Tumor Necrosis Factor-alpha/pharmacology

U2 - 10.1007/s40618-018-0862-8

DO - 10.1007/s40618-018-0862-8

M3 - Article

C2 - 29546654

VL - 41

SP - 1275

EP - 1282

JO - Journal of Endocrinological Investigation

JF - Journal of Endocrinological Investigation

SN - 0391-4097

IS - 11

ER -