15-Lipoxygenase-1 Has Anti-Tumorigenic Effects in Colorectal Cancer

Prostaglandins Leukot Essent Fatty Acids. 2004 Jan;70(1):7-15. doi: 10.1016/j.plefa.2003.06.001.

Abstract

The localization of 15-lipoxygenase-1 (15-LO-1) in human colorectal carcinoma and normal adjacent tissue was examined using immunohistochemistry. In normal tissues, 15-LO-1 was strongly localized in the mucosal epithelium. Conversely, in tumor tissues, staining for 15-LO-1 was dispersed throughout the tissue, weak in neoplastic epithelium, and strong in stromal inflammatory cells. The addition of 50 microM 13(S)-hydroxyeicosatetraenoic acid (HODE), resulted in decreased cell proliferation after 72 h, but lower concentrations (5 or 10 microM) had no effect compared to vehicle treated Caco-2 cells. In addition, 13(S)-HODE had no effect on apoptosis or differentiation of the Caco-2 cells. Microarray analyses of RNA from Caco-2 cells treated with 5 microM 13(S)-HODE revealed changes in 17 genes. HCT-116 colorectal cells were stably transfected with 15-LO-1. In athymic nude mice, transplantable tumors derived from 15-LO-1 HCT-116 cells were smaller than tumors derived from vector HCT-116 cells. These data demonstrate that 13(S)-HODE induces changes in gene expression and has anti-tumorigenic effects.

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism*
  • Apoptosis / drug effects
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Caco-2 Cells
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunohistochemistry
  • Inflammation / enzymology
  • Inflammation / pathology
  • Linoleic Acids / pharmacology
  • Male
  • Mice
  • Neoplasm Transplantation
  • Oligonucleotide Array Sequence Analysis

Substances

  • Antineoplastic Agents
  • Linoleic Acids
  • 13-hydroxy-9,11-octadecadienoic acid
  • Arachidonate 15-Lipoxygenase