Decrease in uptake of arachidonic acid by indomethacin in LS174T human colon cancer cells; a novel cyclooxygenase-2-inhibition-independent effect.
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.
Orido
Takashi
T
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan.
Fujino
Hiromichi
H
Kawashima
Tatsuo
T
Murayama
Toshihiko
T
D016718:Arachidonic Acid / Q000378:metabolism*; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D047495:PPAR gamma / Q000378:metabolism
D018955:CD36 Antigens; D052246:Cyclooxygenase 2 Inhibitors; D050612:Fatty Acid Transport Proteins; D047495:PPAR gamma; D016718:Arachidonic Acid; D007213:Indomethacin