Cancer Res Treat.  2001 Oct;33(5):404-413.

Effects of Cyclooxygenase and Lipoxygenase Inhibitors on the Proliferation of Colon Cancer Cells and Their Production of Eicosanoids

• Lee HS
• Kim EJ
• Oh YS
• Cho HJ
• Park JH

Abstract

PURPOSE: Epidemiological and laboratory studies suggest that nonsteroidal antiinflammatory drugs (NSAIDs) reduce the risk of colon cancer and that the inhibition of colon cancer is mediated through modulation of eicosanoid production. The present study examined the effect of cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors on colon cancer cell growth and prostaglandin E(2) (PGE(2)) or leukotriene B(4) (LTB(4)) secretion by these cells.
MATERIALS AND METHODS
The human colon adenocarcinoma cell lines, Caco-2 and HT-29 cells, were cultured in serum-free medium with various concentrations of indomethacin, piroxicam or esculetin in the presence of 0.15nM or 10nM linoleic acid. Cell number was estimated by MTT assay and PGE(2) and LTB(4) were analyzed by enzyme immunoassay.
RESULTS
The NSAIDs inhibited cell proliferation in a concentration-dependent manner. However, the potency and efficacy of each drug varied in the two cell lines. In Caco-2 cells, the effect of esculetin was higher than that of indomethacin, and piroxicam had no effect. In HT-29 cells, only indomethacin significantly inhibited cell proliferation. All three agents inhibited PGE(2) secretion in a dose-dependent manner; the effect of indomethacin was highest and that of esculetin lowest. The secretion of LTB4 was increased by indomethacin and piroxicam but decreased by esculetin. The effects of these drugs on cell proliferation and eicosanoid secretion were not influenced by linoleic acid concentrations in the culture media. Neither exogenous PGE2 nor LTB4 affected cell proliferation. The results of Pearson correlation analyses revealed that changes in cell proliferation were somewhat related to both concentrations of NSAIDs in the culture medium and production of PGE(2) and LTB(4).
CONCLUSION
The present data suggests that the anti-proliferative effect of NSAIDs may not be entirely attributed to changes in the production of PGE2 and/or LTB4 in the two colon cancer cell lines. These NSAIDs may inhibit cell proliferation largely independent of their ability to modulate eicosanoid synthesis.

Keyword

Colon neoplasm; Cyclooxygenase inhibitor; Lipoxygenase inhibitor; Eicosanoid

MeSH Terms

Adenocarcinoma
Anti-Inflammatory Agents, Non-Steroidal
Caco-2 Cells
Cell Count
Cell Line
Cell Proliferation
Colon*
Colonic Neoplasms*
Culture Media
Dinoprostone
Eicosanoids*
HT29 Cells
Humans
Immunoenzyme Techniques
Indomethacin
Leukotriene B4
Linoleic Acid
Lipoxygenase Inhibitors*
Lipoxygenase*
Piroxicam
Prostaglandin-Endoperoxide Synthases*
Anti-Inflammatory Agents, Non-Steroidal
Culture Media
Dinoprostone
Eicosanoids
Indomethacin
Leukotriene B4
Linoleic Acid
Lipoxygenase
Lipoxygenase Inhibitors
Piroxicam
Prostaglandin-Endoperoxide Synthases