TY - JOUR
T1 - Micromolar concentrations of 2-methoxyestradiol kill glioma cells by an apoptotic mechanism, without destroying their microtubule cytoskeleton
AU - Chamaon, K.
AU - Stojek, J.
AU - Kanakis, D.
AU - Braeuninger, S.
AU - Kirches, Elmar
AU - Krause, G.
AU - Mawrin, C.
AU - Dietzmann, K.
PY - 2005/3
Y1 - 2005/3
N2 - 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 20μM 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 20μM 2-methoxyestradiol after 6 days. A concentration of 0.2 μM 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.
AB - 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 20μM 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 20μM 2-methoxyestradiol after 6 days. A concentration of 0.2 μM 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.
KW - 2-methoxyestradiol
KW - Glioblastoma
KW - Glioma
KW - Microtiter-tetrazolium assay
KW - Microtubules
KW - Proliferation
UR - http://www.scopus.com/inward/record.url?scp=21244482124&partnerID=8YFLogxK
U2 - 10.1007/s11060-004-2158-4
DO - 10.1007/s11060-004-2158-4
M3 - Article
C2 - 15803369
AN - SCOPUS:21244482124
SN - 0167-594X
VL - 72
SP - 11
EP - 16
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 1
ER -