Micromolar concentrations of 2-methoxyestradiol kill glioma cells by an apoptotic mechanism,without destroying their microtubule cytoskeleton |
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Authors: | K?Chamaon J?Stojek D?Kanakis S?Braeuninger Email author" target="_blank">E?KirchesEmail author G?Krause C?Mawrin K?Dietzmann |
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Institution: | (1) Department of Neuropathology, University of Magdeburg, Magdeburg, Germany;(2) Institut für Neuropathologie, Universit¨t of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany |
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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![thinsp](/content/j714j78678l42675/xxlarge8201.gif) M 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![thinsp](/content/j714j78678l42675/xxlarge8201.gif) M 2-methoxyestradiol after 6 days. A concentration of 0.2![thinsp](/content/j714j78678l42675/xxlarge8201.gif) M 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.
K. Chamaon: These authors contributed equally to the work.J. Stojek: These authors contributed equally to the work. |
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Keywords: | glioblastoma glioma 2-methoxyestradiol microtubules Microtiter-tetrazolium assay proliferation |
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