Abstract
Although the influence of selective cyclooxygenase (COX)-2 inhibitors on the proliferation of colon adenocarcinoma cells have been the subject of much investigation, relatively little research has compared the effects of different COX-2 inhibitors. Celecoxib strongly suppressed the proliferation of COX-2 expressing HT-29 cells at 10-40 microM. NS-398 and nimesulide also inhibited cell proliferation, whereas rofecoxib, meloxicam, and etodolac did not. Only celecoxib induced apoptosis of HT-29 cells, as detected on the basis of DNA fragmentation, TUNEL positivity, and caspase-3/7 activation. DNA fragmentation was also increasd in COX-2 non-expressing cell lines (SW-480 and HCT-116) by exposure to celecoxib for 6-24 h. All six COX-2 inhibitors suppressed the production of prostaglandin E(2) by HT-29 cells, suggesting that the pro-apoptotic effect of celecoxib was unrelated to inhibition of COX-2. Inactivation of Akt might explain the differential pro-apoptotic effect of these selective COX-2 inhibitors on colon adenocarcinoma cells.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenocarcinoma / drug therapy*
-
Adenocarcinoma / metabolism
-
Adenocarcinoma / pathology
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
-
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
-
Anticarcinogenic Agents / pharmacology*
-
Anticarcinogenic Agents / therapeutic use
-
Apoptosis*
-
Caspases / metabolism
-
Cell Division / drug effects
-
Colonic Neoplasms / drug therapy*
-
Colonic Neoplasms / metabolism
-
Colonic Neoplasms / pathology
-
Cyclooxygenase 2
-
Cyclooxygenase 2 Inhibitors
-
Cyclooxygenase Inhibitors / pharmacology*
-
Cyclooxygenase Inhibitors / therapeutic use
-
Dinoprostone / biosynthesis
-
Dose-Response Relationship, Drug
-
Humans
-
Isoenzymes / antagonists & inhibitors*
-
Membrane Proteins
-
Prostaglandin-Endoperoxide Synthases
-
Protein Serine-Threonine Kinases*
-
Proto-Oncogene Proteins / metabolism
-
Proto-Oncogene Proteins c-akt
-
Tumor Cells, Cultured
Substances
-
Anti-Inflammatory Agents, Non-Steroidal
-
Anticarcinogenic Agents
-
Cyclooxygenase 2 Inhibitors
-
Cyclooxygenase Inhibitors
-
Isoenzymes
-
Membrane Proteins
-
Proto-Oncogene Proteins
-
Cyclooxygenase 2
-
PTGS2 protein, human
-
Prostaglandin-Endoperoxide Synthases
-
AKT1 protein, human
-
Protein Serine-Threonine Kinases
-
Proto-Oncogene Proteins c-akt
-
Caspases
-
Dinoprostone