Cyclo-oxygenase 2 inhibitor, nabumetone, inhibits proliferation in chronic myeloid leukemia cell lines

Leuk Lymphoma. 2005 May;46(5):753-6. doi: 10.1080/10428190400027860.

Abstract

The anti-tumor effect of cyclo-oxygenase (COX) inhibitors has been documented in several studies. COX2 inhibitors have attracted more attention because of the fewer side-effects and the more prominent anti-tumor effects. However, experience with these drugs in hematological malignancies is limited. In our study, a potent COX2 inhibitor, nabumetone (NBT), was investigated for its anti-proliferative and apoptotic effects in K-562 and Meg-01 chronic myeloid leukemia blastic cell lines as a single agent or in combination with adriamycin (ADR) and interferon alpha (IFN-a). In these cell lines, a dose-dependent inhibition of proliferation was observed with NBT. We observed no significant apoptotic effect of NBT. However, NBT potentiated the apoptotic effect of ADR in the K-562 cell line. Bcl-2 expression was reduced by NBT (11% vs. 2%). The combination of NBT with IFN did not have any significant effect on the K-562 cell line. We suggest that NBT inhibits proliferation and potentiates the apoptotic effect of ADR in chronic myeloid leukemia cell lines.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Butanones / pharmacology*
  • Cell Line, Tumor
  • Cyclooxygenase Inhibitors / pharmacology*
  • Doxorubicin / administration & dosage
  • Drug Screening Assays, Antitumor
  • Flow Cytometry
  • Humans
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Nabumetone
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis

Substances

  • Antineoplastic Agents
  • Butanones
  • Cyclooxygenase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Doxorubicin
  • Nabumetone