Polyamines reverse non-steroidal anti-inflammatory drug-induced toxicity in human colorectal cancer cells

被引:28
|
作者
Hughes, A
Smith, NI
Wallace, HM
机构
[1] Univ Aberdeen, Dept Med, Aberdeen AB25 2ZD, Scotland
[2] Univ Aberdeen, Dept Therapeut, Aberdeen AB25 2ZD, Scotland
[3] Univ Aberdeen, Dept Biomed Sci, Aberdeen AB25 2ZD, Scotland
关键词
apoptosis; colorectal cancer; chemoprevention; non-steroidal anti-inflammatory drug; polyamine; spermidine; spermine;
D O I
10.1042/BJ20030280
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Naproxen, sulindac and salicylate, three NSAIDs (nonsteroidal anti-inflammatory drugs), were cytotoxic to human colorectal cancer cells in culture. Toxicity was accompanied by significant depletion of intracellular polyamine content. Inhibition of ornithine decarboxylase (the first enzyme of the polyamine biosynthetic pathway), induction of polyamine oxidase and spermidine/spermine N'-acetyltransferase (the enzymes responsible for polyamine catabolism) and induction of polyamine export all contributed to the decreased intracellular polyamine content. Morphological examination of the cells showed typical signs of apophosis, and this was confirmed by DNA fragmentation and measurement of caspase-3-like activity. Re-addition of spermidine to the cells partially prevented apoptosis and recovered the cell number. Thus polyamines appear to be an integral part of the signalling pathway mediating NSAID toxicity in human colorectal cancer cells, and may therefore also be important in cancer chemoprevention in humans.
引用
收藏
页码:481 / 488
页数:8
相关论文
共 50 条
  • [31] Rescue strategies against non-steroidal anti-inflammatory drug-induced gastroduodenal damage
    Lim, Yun Jeong
    Lee, Jeong Sang
    Ku, Yang Suh
    Hahm, Ki-Baik
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2009, 24 (07) : 1169 - 1178
  • [32] NON-STEROIDAL ANTI-INFLAMMATORY DRUG-INDUCED DISEASE IN THE DISTAL ILEUM AND LARGE BOWEL
    AABAKKEN, L
    OSNES, M
    SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1989, 24 : 48 - 55
  • [33] NON-STEROIDAL ANTI-INFLAMMATORY DRUG-INDUCED SMALL INTESTINAL STRICTURES - RADIOLOGICAL FEATURES
    LEVI, S
    BJARNASON, I
    DELACEY, G
    PRICE, A
    BURKE, M
    GUMPEL, M
    LEVI, AJ
    GUT, 1989, 30 (05) : A721 - A721
  • [34] Efficacy and safety of rabeprazole in non-steroidal anti-inflammatory drug-induced ulcer in Japan
    Yuji Mizokami
    World Journal of Gastroenterology, 2009, 15 (40) : 5097 - 5102
  • [35] Unmet Needs in Non-steroidal Anti-inflammatory Drug-induced Upper Gastrointestinal Diseases
    James M. Scheiman
    Drugs, 2006, 66 (Suppl 1) : 15 - 21
  • [36] Unmet needs in non-steroidal anti-inflammatory drug-induced upper gastrointestinal diseases
    Scheiman, JM
    DRUGS, 2006, 66 : 15 - 21
  • [37] RANITIDINE MAINTENANCE TREATMENT OF NON-STEROIDAL ANTI-INFLAMMATORY DRUG-INDUCED DUODENAL ULCERATION
    PENSTON, JG
    WORMSLEY, KG
    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 1989, 3 (05) : 499 - 503
  • [38] Clinical, endoscopic and pathologic spectrum of non-steroidal anti-inflammatory drug-induced colitis
    Geramizadeh B.
    Taghavi A.
    Banan B.
    Indian Journal of Gastroenterology, 2009, 28 (4) : 150 - 153
  • [39] Non-steroidal anti-inflammatory drug toxicity in the upper gastrointestinal tract
    Sung, JJY
    Russell, RI
    Yeomans, N
    Chan, FKL
    Chen, SL
    Fock, KM
    Goh, KL
    Kullavanijaya, P
    Kimura, K
    Lau, CS
    Louw, J
    Sollano, J
    Triadiafalopulos, G
    Xiao, SD
    Brooks, P
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2000, 15 : G58 - G68
  • [40] Valdecoxib, a non-steroidal anti-inflammatory drug
    Sony, SMM
    Charles, P
    Ponnuswamy, MN
    Yathirajan, HS
    ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, 2005, 61 : O108 - O110