title: Novel histone deacetylase inhibitors induce growth arrest, apoptosis, and differentiation in sarcoma cancer stem cells.
abstract: Musculoskeletal sarcomas are aggressive malignancies of bone and soft tissues often affecting children and adolescents. Histone deacetylase inhibitors (HDACi) have been proposed to counteract cancer stem cells (CSCs) in solid neoplasms. When tested in human osteosarcoma, rhabdomyosarcoma, and Ewing's sarcoma stem cells, the new HDACi MC1742 (1) and MC2625 (2) increased acetyl-H3 and acetyl-tubulin levels and inhibited CSC growth by apoptosis induction. At nontoxic doses, 1 promoted osteogenic differentiation. Further investigation with 1 will be done in preclinical sarcoma models.
authors.affiliation: †Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), 40136 Bologna, Italy.|‡Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy.
authors.forename: Gemma
authors.initials: G
authors.lastname: Di Pompo
authors.affiliation: †Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), 40136 Bologna, Italy.|‡Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Salerno
authors.affiliation: §Department of Drug Chemistry and Technologies, Sapienza University of Roma, P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.affiliation: §Department of Drug Chemistry and Technologies, Sapienza University of Roma, P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Valente
authors.affiliation: §Department of Drug Chemistry and Technologies, Sapienza University of Roma, P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Clemens
authors.initials: C
authors.lastname: Zwergel
authors.affiliation: †Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), 40136 Bologna, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Avnet
authors.affiliation: ∥Institute of Molecular Genetics, Unit of Bologna IOR, National Research Council of Italy, 40136 Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lattanzi
authors.affiliation: †Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), 40136 Bologna, Italy.|‡Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldini
authors.affiliation: §Department of Drug Chemistry and Technologies, Sapienza University of Roma, P.le A. Moro 5, 00185 Roma, Italy.|⊥Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of Roma, P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D010012:Osteogenesis; D012516:Osteosarcoma / Q000473:pathology; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012208:Rhabdomyosarcoma / Q000473:pathology; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology*; D012512:Sarcoma, Ewing / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000631:Aminopyridines; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C000599961:MC1742; C000599962:MC2625; D011744:Pyrimidinones