Micromolar Concentrations of 2-methoxyestradiol Kill Glioma Cells by an Apoptotic Mechanism, Without Destroying Their Microtubule Cytoskeleton

J Neurooncol. 2005 Mar;72(1):11-6. doi: 10.1007/s11060-004-2158-4.

Abstract

The purpose of this study was to investigate the potential effects of 2-methoxyestradiol, a natural mammalian steroid, in glioma cells, since antiproliferative effects of this compound had been shown earlier in several leukemia and carcinoma cell lines. The effects of 0.2, 2 and 20 microM concentrations of 2-methoxyestradiol were measured in three malignant human glioma cell lines (U87MG, U138MG, LN405) and one malignant rat glioma cell line (RG-2) using a microtiter-tetrazolium (MTT) assay. In all cell lines, a significant reduction of the viable cell number by more then 75% occurred ( P < 0.05) for concentrations of 2 and 20 microM 2-methoxyestradiol after 6 days. A concentration of 0.2 microM had smaller effects (10-40% cell reduction), which were significant in two of the cell lines tested. The apoptotic nature of cell death was further analyzed in U87MG and RG-2 cells. Caspase-3 activity was significantly induced to levels between 3.4- and 23-fold after 4 days for the two higher 2-methoxyestradiol concentrations (P < 0.05). In the cell line RG-2 nuclear fragmentation was visible in many nuclei, following stains with Hoechst H33258. A round cell morphology occurred in most treated cells, which was not accompanied by a complete destruction of the microtubule network, as it can be observed with other microtubule targeting drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Methoxyestradiol
  • Analysis of Variance
  • Animals
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Apoptosis / drug effects*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Caspase 3
  • Caspases / drug effects
  • Cell Line, Tumor
  • Cell Nucleus / pathology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytoskeleton / pathology
  • Dose-Response Relationship, Drug
  • Estradiol / administration & dosage*
  • Estradiol / analogs & derivatives*
  • Estradiol Congeners / administration & dosage*
  • Glioma / drug therapy
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Microtubules / pathology*
  • Rats

Substances

  • Antineoplastic Agents, Hormonal
  • Estradiol Congeners
  • Estradiol
  • 2-Methoxyestradiol
  • CASP3 protein, human
  • Casp3 protein, rat
  • Caspase 3
  • Caspases