Expression of 5-lipoxygenase by Human Colorectal Carcinoma Caco-2 Cells During Butyrate-Induced Cell Differentiation

Biochem Biophys Res Commun. 2000 Feb 24;268(3):778-83. doi: 10.1006/bbrc.2000.2213.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Lipoxygenase-Activating Proteins
  • Arachidonate 5-Lipoxygenase / genetics*
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Butyric Acid / pharmacology*
  • Caco-2 Cells
  • Carrier Proteins / antagonists & inhibitors
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase Inhibitors / pharmacology
  • Humans
  • Hydroxyeicosatetraenoic Acids / metabolism
  • Lipoxygenase Inhibitors / pharmacology
  • Membrane Proteins / antagonists & inhibitors
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation / drug effects

Substances

  • 5-Lipoxygenase-Activating Proteins
  • ALOX5AP protein, human
  • Carrier Proteins
  • Cyclooxygenase Inhibitors
  • Hydroxyeicosatetraenoic Acids
  • Lipoxygenase Inhibitors
  • Membrane Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Transforming Growth Factor beta
  • Butyric Acid
  • 5-hydroxy-6,8,11,14-eicosatetraenoic acid
  • 15-hydroxy-5,8,11,13-eicosatetraenoic acid
  • Arachidonate 5-Lipoxygenase