Decrease in uptake of arachidonic acid by indomethacin in LS174T human colon cancer cells; a novel cyclooxygenase-2-inhibition-independent effect

被引:15
作者
Orido, Takashi [1 ]
Fujino, Hiromichi [1 ]
Kawashima, Tatsuo [2 ]
Murayama, Toshihiko [1 ]
机构
[1] Chiba Univ, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Chuo Ku, Chiba 2608675, Japan
[2] Toho Univ, Sch Med, Sukura Hosp, Dept Internal Med, Sakura 2858741, Japan
基金
日本学术振兴会;
关键词
NSAID; Indomethacin; Arachidonic acid; FAT/CD36; PPAR gamma; ACTIVATED RECEPTOR-GAMMA; HUMAN COLORECTAL-CANCER; PPAR-GAMMA; FATTY-ACIDS; EXPRESSION; PREVENTION; CYCLOOXYGENASE-2; APOPTOSIS; INSULIN; TARGET;
D O I
10.1016/j.abb.2009.11.025
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
Nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive activity and may be suitable for treatment of colorectal cancer. A Popular and potent NSAID, indomethacin, is known to cause serious side-effects, for this reason its therapeutic usefulness is limited. However, these side-effects are likely to be attributed to the additional effects of indomethacin besides its cyclooxygenase inhibition. In this Study, we examined the effect of indomethacin on arachidonic acid uptake using LS174T human colon cancer cells. We here show that treatment of LS174T cells with indomethacin reduced arachidonic acid uptake as well as reduced expressions of fatty acid translocase/CD36 and peroxisome proliferators-activated receptor gamma. Since arachidonic acid is a major substrate of inflammatory mediators Such as prostaglandins and leukotrienes, we believe this novel effect of indomethacin may apply to new treatment strategies that aim to Suppress these mediators by decreasing the uptake of their Substrates, which Would eventually inhibit colorectal cancer malignancy. (C) 2009 Elsevier Inc. All rights reserved.
引用
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页码:78 / 85
页数:8
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