title: LLW-3-6 and celecoxib impacts growth in prostate cancer cells and subcellular localization of COX-2.
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.
authors.affiliation: Department of Biology, Spelman College, Atlanta, GA, U.S.A.
authors.forename: Tokunbo
authors.initials: T
authors.lastname: Yerokun
authors.affiliation: Department of Chemistry & Biochemistry, Spelman College, Atlanta, GA, U.S.A. lwinfield@spelman.edu.
authors.forename: Leyte L
authors.initials: LL
authors.lastname: Winfield
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001562:Benzimidazoles; D052246:Cyclooxygenase 2 Inhibitors; C000592933:LLW-3-6; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib
keywords: Benzimidazole; COX-2; MDA-PCa 2b; PC3; celecoxib; docking; focal adhesion; prostate cancer; sulfasalazine