Expression of 5-lipoxygenase by human colorectal carcinoma Caco-2 cells during butyrate-induced cell differentiation

Butyrate, a short-chain fatty acid, modulates proliferation and differentia tion of normal and neoplastic colonocytes. We examined the expression of B- 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 c omparison 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 metab olic product (5-HETE) was detectable neither in control nor in treated cell s. In contrast, 15-HETE (a product of 15-LO, which is also upregulated by b utyrate) rose significantly, We conclude that, although being overexpressed by butyrate on mRNA and protein level, 5-LO remains inactive in differenti ating Caco-2 cells. This is likely to be due either to some associated acti ons of butyrate, or to 5-LO-inhibition by 15-HETE, concomitantly induced by butyrate treatment. (C) 2000 Academic Press.