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

Gemma Di Pompo, Manuela Salerno, Dante Rotili, Sergio Valente, Clemens Zwergel, Sofia Avnet, Giovanna Lattanzi, Nicola Baldini, Antonello Mai

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4073-4079
Number of pages7
JournalJournal of Medicinal Chemistry
Volume58
Issue number9
DOIs
Publication statusPublished - May 14 2015

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Medicine(all)

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