The anti-cancer effects of phenformin in thyroid cancer cell lines and in normal thyrocytes
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Francesca Coperchini1, Laura Croce1,2, Marco Denegri3, Oriana Awwad4, Samuel Tata Ngnitejeu5, Flavia Magri1,6, Luca Chiovato1,6 and Mario Rotondi1,6
1 Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy
2 PHD course in Experimental Medicine, University of Pavia, Pavia, Italy
3 Molecular Cardiology, ICS-Maugeri, Pavia, Italy
4 Department of Biopharmaceutics and Clinical Pharmacy, The University of Jordan, Amman, Jordan
5 Department of General and Minimally Invasive Surgery, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
6 Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
Keywords: phenformin; tumor-microenvironment; thyroid cancer; CXCL8
Received: August 12, 2019 Accepted: September 24, 2019 Published: PUBLISHED_DATE
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.
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