Micromolar concentrations of 2-methoxyestradiol kill glioma cells by an apoptotic mechanism, without destroying their microtubule cytoskeleton.
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.
Chamaon
K
K
Department of Neuropathology, University of Magdeburg, Magdeburg, Germany.
Stojek
J
J
Kanakis
D
D
Braeuninger
S
S
Kirches
E
E
Krause
G
G
Mawrin
C
C
Dietzmann
K
K
D000077584:2-Methoxyestradiol; D000704:Analysis of Variance; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D045166:Estradiol Congeners / Q000008:administration & dosage*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats
D018931:Antineoplastic Agents, Hormonal; D045166:Estradiol Congeners; D004958:Estradiol; D000077584:2-Methoxyestradiol; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases