Selective cyclooxygenase-2 inhibitors show a differential ability to inhibit proliferation and induce apoptosis of colon adenocarcinoma cells

• Published in: FEBS letters Vol. 531; no. 2; pp. 278 - 284
• Main Authors: Yamazaki, Ryuta, Kusunoki, Natsuko, Matsuzaki, Takeshi, Hashimoto, Shusuke, Kawai, Shinichi
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 06.11.2002
• Subjects: Ac-DEVD-CHO, N-acetyl-Asp-Glu-Val-Asp-aldehyde; Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Akt; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Anticarcinogenic Agents - pharmacology; Anticarcinogenic Agents - therapeutic use; Apoptosis; BrdU, 5-bromo-2′-deoxyuridine; Caspases - metabolism; Celecoxib; Cell Division - drug effects; Colon cancer cells; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; COX, cyclooxygenase; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase Inhibitors - therapeutic use; Dinoprostone - biosynthesis; Dose-Response Relationship, Drug; EGF, epidermal growth factor; ELISA, enzyme-linked immunosorbent assay; FAP, familial adenomatous polyposis; FBS, fetal bovine serum; Humans; Isoenzymes - antagonists & inhibitors; Membrane Proteins; NSAIDs, non-steroidal anti-inflammatory drugs; PPARγ, peroxisome proliferator-activated receptor γ; Proliferation; Prostaglandin-Endoperoxide Synthases; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Selective cyclooxygenase-2 inhibitors; Tumor Cells, Cultured; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; BrdU, 5-bromo-2′-deoxyuridine; EGF, epidermal growth factor; FBS, fetal bovine serum; Selective cyclooxygenase-2 inhibitors; COX, cyclooxygenase; Celecoxib; Proliferation; Akt; FAP, familial adenomatous polyposis; NSAIDs, non-steroidal anti-inflammatory drugs; ELISA, enzyme-linked immunosorbent assay; PPARγ, peroxisome proliferator-activated receptor γ; Ac-DEVD-CHO, N-acetyl-Asp-Glu-Val-Asp-aldehyde; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; Colon cancer cells; Apoptosis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)03535-4

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 μM. 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.