Effects of retinoic acid and tumor necrosis factor alpha on GL-15 glioblastoma cells

Neuroreport. 2000 Feb 7;11(2):389-93. doi: 10.1097/00001756-200002070-00033.

Abstract

Glioblastomas are particularly resistant to classical antitumor treatments. Retinoids, which proved effective in the treatment of promyelocytic leukemia, have been used for clinical assays on glioma tumors with only moderate effects; however in some cases they were active in combination with another therapy. These observations prompted us to analyse the efficacy of combining retinoic acid (RA) with a cytokine on a clonal human glioma cell line. On GL-15 cells, RA and tumor necrosis factor alpha (TNFalpha) both reduced the glial fibrillary acidic protein level and DNA synthesis and induced apoptotic pathways, but they were significantly more effective when used together. The up-regulation of the p55 TNF receptors observed during RA exposure might explain this cooperative effect.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis
  • Bucladesine / pharmacology
  • Cell Size / drug effects
  • Culture Media, Serum-Free / pharmacology
  • DNA / biosynthesis
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Fluorescent Antibody Technique
  • Glial Fibrillary Acidic Protein / biosynthesis
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Protein Binding / drug effects
  • RNA, Messenger / metabolism
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thymidine / metabolism
  • Tretinoin / administration & dosage
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Up-Regulation / drug effects

Substances

  • Antigens, CD
  • Culture Media, Serum-Free
  • Glial Fibrillary Acidic Protein
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Tretinoin
  • Bucladesine
  • DNA
  • Tetradecanoylphorbol Acetate
  • Thymidine