Journal Article

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

Imad Shureiqi, Kirk J. Wojno, Judy A. Poore, Ramesh G. Reddy, Micheline J. Moussalli, Stephen A. Spindler, Joel K. Greenson, Daniel Normolle, Ahmed A.K. Hasan, Theodore S. Lawrence and Dean E. Brenner

in Carcinogenesis

Volume 20, issue 10, pages 1985-1995
Published in print October 1999 | ISSN: 0143-3334
Published online October 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.10.1985
Decreased 13-S-hydroxyoctadecadienoic acid levels and 15-lipoxygenase-1 expression in human colon cancers

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13-S-Hydroxyoctadecadienoic acid (13-S-HODE), the product of 15-lipoxygenase (15-LOX) metabolism of linoleic acid, enhances cellular mitogenic responses 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 intracellular 13-S-HODE. 15-LOX-1 and 13-S-HODE were quantified using western blots, ELISA and immunohistochemistry in 18 human colon cancers with paired normal colonic mucosa. Additionally, 15-LOX-1 expression was measured by western blots in three transformed colonic cell lines and in a human umbilical vein endothelial cell line. Next, we evaluated 13-S-HODE effects on cellular proliferation, cell cycle distribution and apoptosis in a transformed colonic cell line (RKO). Cell cycle distributions were measured by flow cytometry and apoptosis was assessed by phase contrast microscopy, electron microscopy, flow cytometry and DNA fragmentation assay. 15-LOX-1 immunohistochemistry staining scores were reduced in tumor tissues (P ≤ 0.0001) and 15-LOX-1 expression was absent in three transformed colonic cell lines. 13-S-HODE levels were also reduced in tumors tissues compared with normal controls by ELISA (median 3.3-fold, P = 0.02) and by immunohistochemistry (P ≤ 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 expression and a reduction in 13-S-HODE intracellular levels; (ii) 13-S-HODE can suppress cell proliferation and induce apoptosis in transformed colonic epithelial cells.

Keywords: DAB, 3,3′-diaminobenzidine; EGF, epidermal growth factor; H&E, hematoxylin and eosin; HRP, horseradish peroxidase; HUVEC, human umbilical vein endothelial cells; 12-S-HETE, 12-S-hydroxyeicosatetraenoic acid; 13-S-HODE, 13-S-hydroxyoctadecadienoic acid; 15-LOX, 15-lipoxygenase; NDGA, nordihydroguaiaretic acid; PBS, phosphate-buffered saline; NaBT, sodium butyrate; SHE, Syrian hamster embryo; TBS, Tris-buffered saline.

Journal Article.  8136 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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