Anticancer effects of licofelone (ML-3000) in prostate cancer cells

Anticancer Res. 2007 Jul-Aug;27(4B):2393-402.

Abstract

Background: Licofelone, a potent antiinflammatory agent has been reported to interfere with the cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) signaling pathways with few side-effects. However, the underlying mechanism of licofelone against human cancer is not understood.

Materials and methods: Human and mouse prostate cancer cells were exposed to licofelone in a time- and dose-dependent manner. Cell growth/cell viability, apoptosis, and expression of COX-2 and 5-LOX at the gene and protein levels were investigated.

Results: For the first time, it was demonstrated that licofelone inhibited prostate cancer cell growth and significantly down-regulated COX-2 and 5-LOX expression. A weak inhibitory effect on COX-1 protein was also observed.

Conclusion: Licofelone inhibited COX-2 and 5-LOX simultaneously and prevented overall cancer cell growth by enhancing apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. Validating the dual role of licofelone in animal models of prostate cancer is critical for promoting its use as a potential chemopreventive or therapeutic agent.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetates / pharmacology*
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Arachidonate 5-Lipoxygenase / biosynthesis
  • Arachidonate 5-Lipoxygenase / genetics
  • Cell Growth Processes / drug effects
  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Lipoxygenase Inhibitors
  • Male
  • Mice
  • Mice, Transgenic
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Pyrroles / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transcription, Genetic / drug effects
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Acetates
  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Lipoxygenase Inhibitors
  • Pyrroles
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2
  • licofelone