5-hydroxy-6-8-11-14-eicosatetraenoic-acid and Colorectal-Neoplasms

Butyrate, a short-chain fatty acid, modulates proliferation and differentiation of normal and neoplastic colonocytes. We examined the expression of 5-lipoxygenase (5-LO) and its metabolites in human colorectal carcinoma (Caco-2) cells, exposed to differentiation-inducing doses of butyrate. Treatment with butyrate significantly increased 5-lipoxygenase mRNA and protein in comparison to nontreated cells. Cyclooxygenases (COX)-1 and COX-2 mRNA were not significantly influenced by the treatment. However, 5-LO activity, low in nontreated cells, increased only minimally after butyrate, and its metabolic product (5-HETE) was detectable neither in control nor in treated cells. In contrast, 15-HETE (a product of 15-LO, which is also upregulated by butyrate) rose significantly. We conclude that, although being overexpressed by butyrate on mRNA and protein level, 5-LO remains inactive in differentiating Caco-2 cells. This is likely to be due either to some associated actions of butyrate, or to 5-LO-inhibition by 15-HETE, concomitantly induced by butyrate treatment.

Topics: 5-Lipoxygenase-Activating Proteins; Arachidonate 5-Lipoxygenase; Butyric Acid; Caco-2 Cells; Carrier Proteins; Cell Differentiation; Cell Division; Colorectal Neoplasms; Cyclooxygenase Inhibitors; Humans; Hydroxyeicosatetraenoic Acids; Lipoxygenase Inhibitors; Membrane Proteins; RNA, Messenger; RNA, Neoplasm; Transforming Growth Factor beta; Up-Regulation