Michele Massimino1,2, Elena Tirrò3,2, Stefania Stella3,2, Francesco Frasca4, Veronica Vella5, Laura Sciacca6, Maria Stella Pennisi3,2, Silvia Rita Vitale3,2, Adriana Puma3,2, Chiara Romano3,2, Livia Manzella3,2. 1. Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy michedot@yahoo.it. 2. Center of Experimental Oncology and Hematology, University Hospital Vittorio Emanuele, Catania, Italy. 3. Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy. 4. Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, Catania, Italy. 5. School of Motor Sciences, Faculty of Human and Social Sciences, Kore University of Enna, Enna, Italy. 6. Department of Clinical and Experimental Medicine, Endocrinology Section, University of Catania, Catania, Italy.
Abstract
BACKGROUND: Poorly differentiated (PDTC) and anaplastic thyroid (ATC) cancer cells are characterized by the acquisition of epigenetic abnormalities, leading to the silencing of both the sodium iodide co-transporter and the Coxsackie adenovirus receptor. As aberrant histone acetylation and DNA methylation represent epigenetic mechanisms involved in neoplastic transformation, our study investigated the anticancer properties of epigenetic modifiers in thyroid carcinoma. MATERIALS AND METHODS: The cytotoxicity and gene expression modulation of histone deacetylase and DNA methyltransferase inhibitors were evaluated in both PDTC and ATC. RESULTS: Epigenetic treatments were cytotoxic to tumor thyrocytes and restored sodium iodide co-transporter and Coxsackie adenovirus receptor, expression as well as radioiodine uptake, in PDTC but not in ATC. However, ectopic expression sodium iodide co-transporter re-activated radioiodine incorporation in ATC. CONCLUSION: The ability of epigenetic treatments to interfere with tumor proliferation and induce Coxsackie adenovirus receptor expression, coupled with the ability of ectopic sodium iodide co-transporter to restore radioiodine uptake, raise the possibility that these therapeutic approaches may provide clinical benefit to patients with thyroid carcinoma refractory to radioiodine treatment. Copyright
BACKGROUND: Poorly differentiated (PDTC) and anaplastic thyroid (ATC) cancer cells are characterized by the acquisition of epigenetic abnormalities, leading to the silencing of both the sodium iodide co-transporter and the Coxsackie adenovirus receptor. As aberrant histone acetylation and DNA methylation represent epigenetic mechanisms involved in neoplastic transformation, our study investigated the anticancer properties of epigenetic modifiers in thyroid carcinoma. MATERIALS AND METHODS: The cytotoxicity and gene expression modulation of histone deacetylase and DNA methyltransferase inhibitors were evaluated in both PDTC and ATC. RESULTS: Epigenetic treatments were cytotoxic to tumor thyrocytes and restored sodium iodide co-transporter and Coxsackie adenovirus receptor, expression as well as radioiodine uptake, in PDTC but not in ATC. However, ectopic expression sodium iodide co-transporter re-activated radioiodine incorporation in ATC. CONCLUSION: The ability of epigenetic treatments to interfere with tumor proliferation and induce Coxsackie adenovirus receptor expression, coupled with the ability of ectopic sodium iodide co-transporter to restore radioiodine uptake, raise the possibility that these therapeutic approaches may provide clinical benefit to patients with thyroid carcinoma refractory to radioiodine treatment. Copyright
Authors: Michele Massimino; Paolo Vigneri; Stefania Stella; Elena Tirrò; Maria Stella Pennisi; Laura Nunziatina Parrinello; Calogero Vetro; Livia Manzella; Fabio Stagno; Francesco Di Raimondo Journal: J Clin Med Date: 2021-11-29 Impact factor: 4.241
Authors: Livia Manzella; Elena Tirrò; Silvia Rita Vitale; Adriana Puma; Maria Letizia Consoli; Loredana Tambè; Maria Stella Pennisi; Sandra DI Gregorio; Chiara Romano; Cristina Tomarchio; Francesco DI Raimondo; Fabio Stagno Journal: In Vivo Date: 2020 May-Jun Impact factor: 2.155