title: Different cell cycle modulation by celecoxib at different concentrations.
abstract: Abstract Different cyclooxygenase (COX)-2 inhibitors were known to cause different cell cycle changes. We investigated whether this different effect on cell cycle change was due to concentration-dependent effect. We investigated the effects of celecoxib, a COX-2 selective inhibitor, on cell cycle regulation in irradiated cancer cells that express high or low levels of COX-2. Four stably COX-2 knocked-down or overexpressed cell lines were treated with various concentrations of celecoxib with or without radiation. Celecoxib differentially modulated the cell cycle according to the concentrations applied. G1 arrest was induced at lower concentrations, whereas G2/M arrest was induced at higher concentrations in each cell line tested. Radiation-induced G2/M arrest was enhanced at lower concentrations but reduced at higher concentrations. The cutoff values to divide lower and higher concentrations were cell-type specific. Celecoxib treatment activated Cdc25C and inhibited p21 expression in both unirradiated and irradiated cells, regardless of COX-2 expression. Apoptosis was induced in irradiated cells 48 hours after treatment with celecoxib dependent of COX-2. These results imply that celecoxib deactivates the G2 checkpoint via both Cdc25C- and p21-dependent pathways in irradiated cells, which subsequently die by secondary apoptosis. Cell cycle modulating effects in irradiated cells resulting from treatment with celecoxib may have clinical importance with regard to the potential application of celecoxib in cancer patients undergoing radiotherapy.
authors.affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Young-Mee
authors.initials: YM
authors.lastname: Kim
authors.forename: Hongryull
authors.initials: H
authors.lastname: Pyo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011720:Pyrazoles / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D034741:RNA, Small Interfering; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib