Decreased 13-S-hydroxyoctadecadienoic acid levels and 15-lipoxygenase-1 expression in human colon cancers

13-S-Hydroxyoctadecadienoic acid (13-S-HODE), the product of 15-lipoxygenas e (15-LOX) metabolism of linoleic acid, enhances cellular mitogenic respons es to certain growth factors. Other observations have questioned whether 13 -S-HODE has tumorigenic effects. Our study evaluated the hypothesis that 15 -LOX-1 is overexpressed in colon cancers resulting in an increase in intrac ellular 13-S-HODE, 15-LOX-1 and 13-S-HODE were quantified using western blo ts, ELISA and immunohistochemistry in 18 human colon cancers with paired no rmal colonic mucosa. Additionally, 15-LOX-1 expression was measured by west ern blots in three transformed colonic cell lines and in a human umbilical vein endothelial cell line. Next, we evaluated 13-S-HODE effects on cellula r proliferation, cell cycle distribution and apoptosis in a transformed col onic cell line (RKO). Cell cycle distributions were measured by flow cytome try and apoptosis was assessed by phase contrast microscopy, electron micro scopy, flow cytometry and DNA fragmentation assay. 15-LOX-1 immunohistochem istry staining scores were reduced in tumor tissues (P less than or equal t o 0.0001) and 15-LOX-1 expression was absent in three transformed colonic c ell lines. 13-S-HODE levels were also reduced in tumors tissues compared wi th normal controls by ELISA (median 3.3-fold, P = 0.02) and by immunohistoc hemistry (P less than or equal to 0.0001). In vitro 13-S-HODE inhibited RKO cell proliferation and induced cell cycle arrest and apoptosis, 13-S-HODE produced similar effects in HT-29 cells. Our observations indicate that: (i ) human colon cancers are associated with a down-regulation in 15-LOX-1 exp ression and a reduction in 13-S-HODE intracellular levels; (ii) 13-S-HODE c an suppress cell proliferation and induce apoptosis in transformed colonic epithelial cells.