The compound 13-D selectively induces apoptosis in white blood cancers versus other cancer cell types

Karson S. Putt, Vitaliy Nesterenko, Robin S. Dothager, Paul J. Hergenrother

Research output: Contribution to journalArticlepeer-review

Abstract

As general cytotoxins are still the backbone of anticancer chemotherapy, the identification of selective inducers of cell death in defined cancer types and subtypes is one of the major goals of modern oncology research. Thus, compounds identified with such selectivity have utility as probes of cancer-type-specific biological pathways, and optimized versions have potential in targeted anticancer therapy. Described herein is the discovery that compound 13-D selectively induces apoptotic cell death in white blood cancer cell lines but not in other cancer cell lines. Further experiments indicate that this selectivity is not simply due to selective cell permeability. The compound localizes to both the nucleus and cytoplasm and arrests cells in the prophase/prometaphase of the cell cycle, and there is a very sharp dependence of activity on compound structure, with the trans-α,β-unsaturated amide of 13-D being critical for inducing cell death. The macromolecular target of 13-D could be involved in white blood cell-specific oncogenic pathways.

Original languageEnglish (US)
Pages (from-to)1916-1922
Number of pages7
JournalChemBioChem
Volume7
Issue number12
DOIs
StatePublished - Dec 1 2006

Keywords

  • Apoptosis
  • Bioorganic chemistry
  • Cancer
  • Cell cycle
  • White blood cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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