LLW-3-6 and celecoxib impacts growth in prostate cancer cells and subcellular localization of COX-2

Anticancer Res. 2014 Sep;34(9):4755-9.

Abstract

The proliferation in human prostate carcinomas, PC3 and MDA-PCa-2b, was analyzed for cells treated with LLW-3-6 and celecoxib in the presence and absence of sulfasalazine. LLW-3-6 was more potent than celecoxib at mediating a dose-dependent reduction of viable PC3 cells. Co-treatment with a non-lethal dose of sulfasalazine diminished the potency of both drugs in this cell line. The effects of the drugs in MDA-PCa-2b cells were less significant than those observed in the PC3 cells. Localization of COX-2 in LLW-3-6- and CBX-treated PC3 cells is consistent with protein aggregation known for cells responding to stress stimuli. To complement this, an analysis of the theoretical binding interactions of LLW-3-6 was completed to illustrate the potential of LLW-3-6 to bind to COX-2 in a manner similar to that of celecoxib. Studies to further define the mechanism of action for LLW-3-6 are ongoing.

Keywords: Benzimidazole; COX-2; MDA-PCa 2b; PC3; celecoxib; docking; focal adhesion; prostate cancer; sulfasalazine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Celecoxib
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Intracellular Space / metabolism
  • Male
  • Models, Molecular
  • Molecular Conformation
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Protein Binding
  • Protein Transport / drug effects
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Benzimidazoles
  • Cyclooxygenase 2 Inhibitors
  • LLW-3-6
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • Celecoxib