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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminopyridines / chemical synthesis
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Aminopyridines / chemistry*
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Aminopyridines / pharmacology
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Apoptosis / drug effects*
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Bone Neoplasms / pathology
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Cell Differentiation / drug effects*
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Drug Screening Assays, Antitumor
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Histone Deacetylase Inhibitors / chemical synthesis
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Histone Deacetylase Inhibitors / chemistry*
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Histone Deacetylase Inhibitors / pharmacology
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Humans
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Hydroxamic Acids / chemical synthesis
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Hydroxamic Acids / chemistry*
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Hydroxamic Acids / pharmacology
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Neoplastic Stem Cells / drug effects*
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Neoplastic Stem Cells / pathology
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Osteogenesis
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Osteosarcoma / pathology
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Pyrimidinones / chemical synthesis
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Pyrimidinones / chemistry*
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Pyrimidinones / pharmacology
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Rhabdomyosarcoma / pathology
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Sarcoma / drug therapy
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Sarcoma / pathology*
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Sarcoma, Ewing / pathology
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Structure-Activity Relationship
Substances
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Aminopyridines
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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MC1742
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MC2625
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Pyrimidinones