Selective inhibition of Δ-6 desaturase impedes intestinal tumorigenesis

• Published in: Cancer letters 2002-01, Vol.175 (2), p.157-163
• Main Authors: Hansen-Petrik, Melissa B, McEntee, Michael F, Johnson, Benjamin T, Obukowicz, Mark G, Masferrer, Jaime, Zweifel, Ben, Chiu, Chun-Hung, Whelan, Jay
• Format: Article
• Language: English
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; ApcMin/+ mouse; Arachidonic acid; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Enzyme Inhibitors - pharmacology; Fatty Acid Desaturases - antagonists & inhibitors; HT-29 cell; Intestinal Neoplasms - prevention & control; Intestinal tumor; Linoleoyl-CoA Desaturase; Male; Medical sciences; Mice; Mice, Inbred C57BL; Piperazines - pharmacology; SC-26196; Tumors; Δ-6 Desaturase
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(01)00715-7

Arachidonic acid is an important polyunsaturated fatty acid involved in cell signaling. It is derived primarily from dietary linoleic acid, and the rate-limiting step in its biosynthesis is the initial desaturation of linoleic acid via Δ-6 desaturase. Evidence suggests that downstream metabolic products of arachidonic acid, e.g. prostaglandins, are involved in colorectal cancer, but involvement of the biosynthetic pathway of arachidonic acid has not been previously investigated. In the present study, we report the effects of a novel selective Δ-6 desaturase inhibitor, SC-26196, on tumorigenesis in two in vivo models of intestinal cancer. SC-26196 treatment resulted in 36–37% fewer tumors in Apc Min/+ mice and 35% decrease in primary tumor size in nude mice bearing HT-29 human colon cancer cell xenografts ( P