The anti-cancer effects of phenformin in thyroid cancer cell lines and in normal thyrocytes.
CXCL8
phenformin
thyroid cancer
tumor-microenvironment
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
05 Nov 2019
05 Nov 2019
Historique:
received:
12
08
2019
accepted:
24
09
2019
entrez:
20
11
2019
pubmed:
20
11
2019
medline:
20
11
2019
Statut:
epublish
Résumé
Phenformin is a biguanide drug which, besides the original anti-diabetic effect, also exerts anti-cancer effects. The aim of this study was to further characterize these latter in terms of both cell-viability and modulation of the secretion of the pro-tumorigenic chemokine CXCL8. Normal human thyrocytes in primary cultures (NHT) and thyroid cancer cell lines, TPC-1 and 8505C (RET/PTC and BRAFV600E mutated, respectively) were treated with increasing concentrations of phenformin at different times. Cell-viability was assessed by WST-1 and further characterized by AnnexinV/PI staining and cell proliferation colony-assay. CXCL8 levels were measured in cell supernatants. Phenformin reduced cell-viability in TPC-1 and 8505C and their ability to form colonies. In NHT cells, phenformin affected cell-viability only at the maximal dose but interestingly it inhibited CXCL8 secretion at all the concentrations not affecting cell-viability. Phenformin had no effect on CXCL8 secretion in thyroid cancer cell lines. Thus, phenformin exerts anti-cancer effects on both cancer cells (cell death induction) and surrounding normal cells (inhibition of CXCL8 secretion). These results highlight that the anti-cancer effects of phenformin are multifaceted and effective on both solid and soluble components of the tumor-microenvironment.
Identifiants
pubmed: 31741708
doi: 10.18632/oncotarget.27266
pii: 27266
pmc: PMC6849649
doi:
Types de publication
Journal Article
Langues
eng
Pagination
6432-6443Informations de copyright
Copyright: © 2019 Coperchini et al.
Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST The authors have nothing to disclose
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