Nandrolone induces a stem cell-like phenotype in human hepatocarcinoma-derived cell line inhibiting mitochondrial respiratory activity.

Autor: Agriesti F; Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy., Tataranni T; Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy., Pacelli C; Department of Clinical and Experimental Medicine, University of Foggia, via L. Pinto c/o OO.RR., 71100, Foggia, Italy., Scrima R; Department of Clinical and Experimental Medicine, University of Foggia, via L. Pinto c/o OO.RR., 71100, Foggia, Italy., Laurenzana I; Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy., Ruggieri V; Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy., Cela O; Department of Clinical and Experimental Medicine, University of Foggia, via L. Pinto c/o OO.RR., 71100, Foggia, Italy., Mazzoccoli C; Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy., Salerno M; Department of Medical, Surgical Sciences and Advanced Technologies 'G.F. Ingrassia', University of Catania - A.O.U. 'Policlinico - V. Emanuele', via S. Sofia, 87 - Sector 10, Building B - 95123, Catania, Italy., Sessa F; Department of Clinical and Experimental Medicine, University of Foggia, via L. Pinto c/o OO.RR., 71100, Foggia, Italy., Sani G; Department of Neuroscience, Section of Psychiatry, Università Cattolica del Sacro Cuore, Roma, Italy.; Department of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy., Pomara C; Department of Medical, Surgical Sciences and Advanced Technologies 'G.F. Ingrassia', University of Catania - A.O.U. 'Policlinico - V. Emanuele', via S. Sofia, 87 - Sector 10, Building B - 95123, Catania, Italy., Capitanio N; Department of Clinical and Experimental Medicine, University of Foggia, via L. Pinto c/o OO.RR., 71100, Foggia, Italy., Piccoli C; Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy. claudia.piccoli@unifg.it.; Department of Clinical and Experimental Medicine, University of Foggia, via L. Pinto c/o OO.RR., 71100, Foggia, Italy. claudia.piccoli@unifg.it.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Feb 10; Vol. 10 (1), pp. 2287. Date of Electronic Publication: 2020 Feb 10.
DOI: 10.1038/s41598-020-58871-1
Abstrakt: Nandrolone is a testosterone analogue with anabolic properties commonly abused worldwide, recently utilized also as therapeutic agent in chronic diseases, cancer included. Here we investigated the impact of nandrolone on the metabolic phenotype in HepG2 cell line. The results attained show that pharmacological dosage of nandrolone, slowing cell growth, repressed mitochondrial respiration, inhibited the respiratory chain complexes I and III and enhanced mitochondrial reactive oxygen species (ROS) production. Intriguingly, nandrolone caused a significant increase of stemness-markers in both 2D and 3D cultures, which resulted to be CxIII-ROS dependent. Notably, nandrolone negatively affected differentiation both in healthy hematopoietic and mesenchymal stem cells. Finally, nandrolone administration in mice confirmed the up-regulation of stemness-markers in liver, spleen and kidney. Our observations show, for the first time, that chronic administration of nandrolone, favoring maintenance of stem cells in different tissues would represent a precondition that, in addition to multiple hits, might enhance risk of carcinogenesis raising warnings about its abuse and therapeutic utilization.
Databáze: MEDLINE
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