5-lipoxygenase pathway promotes cell proliferation in human glioma cell lines

Clin Neuropathol. Nov-Dec 2009;28(6):445-52. doi: 10.5414/npp28445.

Abstract

Objective: 5-lipoxygenase (5-LO) is a key enzyme in the synthesis of leukotrienes (LTs), that might promote carcinogenesis. We investigated 5-LO expression and examined whether the 5-LO pathway is associated with the proliferation of human brain tumors.

Methods: We immunohistochemically evaluated the profile of 5-LO expression in various types of brain tumors obtained from 42 patients, and examined the proliferative effects of the 5-LO pathway in human glioma cell lines using a proliferation assay.

Results: Immunohistochemistry of glioblastomas, astrocytomas, meningiomas, medulloblastomas, craniopharyngiomas, ependymomas, neurinomas, oligodendrogliomas, malignant lymphomas, dysembryoplastic neuroepithelial and metastatic brain tumors revealed 5-LO expression in the cytoplasm and nuclei or nuclear envelopes of tumor cells. The 5-LO inhibitor A861 and the LTA4 hydrolase inhibitor Bestatin dose-dependently suppressed the proliferation of A172 cells, a glioma cell line.

Conclusions: We confirmed the expression of 5-LO in various human brain tumors and demonstrated the partial suppression of tumor growth by inhibitors of the 5-LO-LTA4 hydrolase pathway in human glioma cell lines. The 5-LO-LTA4 pathway might play roles in the proliferation of human glioma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arachidonate 5-Lipoxygenase / physiology*
  • Astrocytoma / pathology
  • Astrocytoma / physiopathology
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / physiopathology
  • Cell Proliferation*
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Female
  • Glioblastoma / pathology
  • Glioblastoma / physiopathology
  • Glioma / pathology*
  • Glioma / physiopathology
  • Humans
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Leukotriene A4 / antagonists & inhibitors
  • Leukotriene A4 / physiology
  • Lipoxygenase Inhibitors
  • Male
  • Meningioma / pathology
  • Meningioma / physiopathology
  • Middle Aged
  • Protease Inhibitors / pharmacology
  • Signal Transduction / physiology*
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Leukotriene A4
  • Lipoxygenase Inhibitors
  • Protease Inhibitors
  • Arachidonate 5-Lipoxygenase
  • Leucine
  • ubenimex