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

FEBS Letters

Kawai, Shinichi¹  Kusunoki, Natsuko¹  Matsuzaki, Takeshi²  Hashimoto, Shusuke²  Yamazaki, Ryuta¹ 

[1]Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8512, Japan

[2]Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan

关键词: Selective cyclooxygenase-2 inhibitors;    Celecoxib;    Proliferation;    Apoptosis;    Colon cancer cells;    Akt;    COX;    cyclooxygenase;    FAP;    familial adenomatous polyposis;    NSAIDs;    non-steroidal anti-inflammatory drugs;    FBS;    fetal bovine serum;    Ac-DEVD-CHO;    N-acetyl-Asp-Glu-Val-Asp-aldehyde;    EGF;    epidermal growth factor;    BrdU;    5-bromo-2′-deoxyuridine;    TUNEL;    terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling;    ELISA;    enzyme-linked immunosorbent assay;    PPARγ;    peroxisome proliferator-activated receptor γ;   

DOI  :  10.1016/S0014-5793(02)03535-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 E₂ 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.

【 授权许可】

Unknown