biostudies-literatureAgriesti FItalian Ministry of Education, University and Research grant FIRBCurrent Research Funds from the Italian Ministry of Health to IRCCS-CROB2287https://www.ebi.ac.uk/biostudies/studies/S-EPMC7010785biostudies-literatureUnknown10(1)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 administScientific reportsNandrolone induces a stem cell-like phenotype in human hepatocarcinoma-derived cell line inhibiting mitochondrial respiratory activity.PMC7010785RBFR12LD0WAgriesti FScrima RPacelli CMazzoccoli CCapitanio NSalerno MCela OLaurenzana IPiccoli CTataranni TRuggieri VPomara CSani GSessa FfalseNandrolone induces a stem cell-like phenotype in human hepatocarcinoma-derived cell line inhibiting mitochondrial respiratory activity.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 administ2020-01-01T00:00:00Z2020 Feb2025-04-22T00:21:11.636Z2020-05-22T10:39:46ZS-EPMC70107853204198310.1038/s41598-020-58871-1