Dup-697, a specific COX-2 inhibitor, suppresses growth and induces apoptosis on K562 leukemia cells by cell-cycle arrest and caspase-8 activation

Ann Hematol. 2008 Feb;87(2):121-9. doi: 10.1007/s00277-007-0385-4. Epub 2007 Nov 13.

Abstract

This investigation was designed to assess the effect of DuP-697 on growth and apoptosis in a human chronic myeloid leukemia (CML) cell line (K562 cells) and primary CML cells from CML patient bone marrow. DuP-697 significantly suppressed K562 cells and primary CML cells growth and induced apoptosis in a concentration-dependent manner and the growth-inhibiting effect was independent on Philadelphia chromosome. The IC50 of DuP-697 at 36 h was 31.7 muM. It arrested G1-S phase transmit on cell cycle and its apoptosis activity was partially abrogated by pretreating K562 cells with Z-IETD-fmk, a specific inhibitor of caspase-8. This study suggested that Dup-697 suppresses growth and induces apoptosis on K562 leukemia cells by cell-cycle arrest and caspase-8 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Bone Marrow Cells / drug effects
  • Caspase 8 / drug effects
  • Caspase 8 / metabolism
  • Cell Cycle / drug effects
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Humans
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Thiophenes / pharmacology*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Thiophenes
  • DuP 697
  • Caspase 8