2. Academic Validation
  3. Novel histone deacetylase inhibitors induce growth arrest, apoptosis, and differentiation in sarcoma cancer stem cells

Novel histone deacetylase inhibitors induce growth arrest, apoptosis, and differentiation in sarcoma cancer stem cells

  • J Med Chem. 2015 May 14;58(9):4073-9. doi: 10.1021/acs.jmedchem.5b00126.
Gemma Di Pompo 1 2,  Manuela Salerno 1 2,  Dante Rotili 3,  Sergio Valente 3,  Clemens Zwergel 3,  Sofia Avnet 1,  Giovanna Lattanzi 4,  Nicola Baldini 1 2,  Antonello Mai 3 5
Affiliations

Affiliations

  • 1 †Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), 40136 Bologna, Italy.
  • 2 ‡Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy.
  • 3 §Department of Drug Chemistry and Technologies, Sapienza University of Roma, P.le A. Moro 5, 00185 Roma, Italy.
  • 4 ∥Institute of Molecular Genetics, Unit of Bologna IOR, National Research Council of Italy, 40136 Bologna, Italy.
  • 5 ⊥Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of Roma, P.le A. Moro 5, 00185 Roma, Italy.
PMID: 25905694 DOI: 10.1021/acs.jmedchem.5b00126
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.

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