Dimethyl-celecoxib (DMC), a derivative of celecoxib that lacks cyclooxygenase-2-inhibitory function, potently mimics the anti-tumor effects of celecoxib on Burkitt's lymphoma in vitro and in vivo

Adel Kardosh, Weijun Wang, Jasim Uddin, Nicos A. Petasis, Florence M. Hofman, Thomas C. Chen, Axel H. Schönthal

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

The nonsteroidal anti-inflammatory drug (NSAID) celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor that has shown some promising results as an anti-cancer drug. However, the question arose as to whether or not its COX-2-inhibitory function is required for its anti-tumorigenic properties. We therefore employed dimethyl-celecoxib (DMC), which is a close structural analog of celecoxib that lacks COX-2-inhibitory function, to investigate this question. By performing a combination of in vitro and in vivo studies with Burkitt's lymphoma cells, we found that DMC potently mimics all of the anti-proliferative and anti-tumorigenic effects of celecoxib. In cell culture, DMC effectively inhibits cell proliferation through the down-regulation of cyclins A and B and the ensuing loss of cyclin-dependent kinase activity. This effect appears to take place in vivo as well and results in significantly (p < .002) reduced tumor growth in experimental animals. Thus, our results demonstrate that the anti-proliferative and anti-tumorigenic properties of celecoxib and DMC are indistinguishable, at least in Burkitt's lymphoma cells, and therefore, that the COX-2-inhibitory function is not required for these effects.

Original languageEnglish (US)
Pages (from-to)571-582
Number of pages12
JournalCancer Biology and Therapy
Volume4
Issue number5
DOIs
StatePublished - May 2005

Keywords

  • Bextra
  • Burkitt's lymphoma
  • CDK
  • Celebrex
  • Celecoxib
  • Cell cycle
  • Cyclins
  • DMC
  • Flurbiprofen
  • Indomethacin
  • Lymphoma
  • NSAIDs
  • Raji
  • Ramos
  • Rofecoxib
  • Sulindac
  • Valdecoxib
  • Vioxx

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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