The anti-cancer effects of phenformin in thyroid cancer cell lines and in normal thyrocytes

// Francesca Coperchini 1 , Laura Croce 1 , 2 , Marco Denegri 3 , Oriana Awwad 4 , Samuel Tata Ngnitejeu 5 , Flavia Magri 1 , 6 , Luca Chiovato 1 , 6 and Mario Rotondi 1 , 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 Correspondence to: Luca Chiovato, email: luca.chiovato@icsmaugeri.it Keywords: phenformin; tumor-microenvironment; thyroid cancer; CXCL8 Received: August 12, 2019     Accepted: September 24, 2019     Published: PUBLISHED_DATE ABSTRACT 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.