Evidence that human epithelial cells express leukotriene receptors

Little is known regarding the potential role of leukotrienes (LTs) in colon carcinogenesis. Recently we observed that LTB4, a lipoxygenase product, increased the proliferation rate of HT-29 human colon carcinoma cells in a time- and concentrationdependent manner. Therefore, we evaluated the possibility that this proliferative effect might be mediated through a specific receptor. HT-29 cells were treated with LTB4 at a concentration of 1 x JO'8 M for 72 hrs in presence or absence of SC-41930, a competitive antagonist of LTB4 receptors. LTB4 caused approximately a 50% increase in the number of HT-29 cells. This increase in proliferation was inhibited by SC-41930 in a concentration-dependent manner, 100% inhibition was achieved by a concentration of 20 x 10'8 M. SC-41930 alone (0.05 -100 x 10-8 M) had no significant effect on the growth rate of these cells over the same time period. CONCLUSIONS: SC-41930 an antagonist of LTB4 receptors inhibited the proliferative effects of LTB4 in human colon cancer cells, suggesting the existence of an LTB4 receptor in epithelial cells. (Funded in part by The Arthur and Rochelle Belfer Foundation Study at The Rockefeller University).