TY - JOUR
T1 - Nanomolar concentrations of epothilone D inhibit the proliferation of glioma cells and severely affect their tubulin cytoskeleton
AU - Dietzmann, A.
AU - Kanakis, D.
AU - Kirches, Elmar
AU - Kropf, S.
AU - Mawrin, C.
AU - Dietzmann, K.
PY - 2003/11
Y1 - 2003/11
N2 - The purpose of this study was to investigate the potential effects of epothilones (EPOs), a new class of microtubule stabilizing cytotoxic drugs, on glioma cells in vitro. The effects of 1, 10 and 100 nM concentrations of EPO D in four malignant human glioma cell lines were measured using a microtiter-tetrazolium assay. Besides the cell lines U87MG, U138MG and LN405, one cell line was used, which had been derived from a recurrent and therapy-resistant glioblastoma in our laboratory. In addition, changes of the cell morphology were followed by light microscopy and changes in the microtubule and actin cytoskeleton were visualized by a confocal laser microscope. In all four human glioma cell lines, 10 and 100 nM concentrations of the drug, applied for 96 h, lead to a highly significant decrease in the viable cell number (p < 0. 001). A mean reduction of the viable cell number between 30% and 40% (60% and 90%) was observed for a drug concentration of 10nM (100nM). A round cell morphology occured in most EPO treated cells and the organized network of microtubules was shrunk in these round cells. The tubulin immunostaining now appeared amorphous and was restricted to small perinuclear regions. Large actin filaments also disappeared, but actin staining was present in the whole cytosplasm. These results prove that EPOs have antiproliferative effects in glioma cells and affect their tubulin cytoskeleton, as it was previously observed in several types of carcinoma cells.
AB - The purpose of this study was to investigate the potential effects of epothilones (EPOs), a new class of microtubule stabilizing cytotoxic drugs, on glioma cells in vitro. The effects of 1, 10 and 100 nM concentrations of EPO D in four malignant human glioma cell lines were measured using a microtiter-tetrazolium assay. Besides the cell lines U87MG, U138MG and LN405, one cell line was used, which had been derived from a recurrent and therapy-resistant glioblastoma in our laboratory. In addition, changes of the cell morphology were followed by light microscopy and changes in the microtubule and actin cytoskeleton were visualized by a confocal laser microscope. In all four human glioma cell lines, 10 and 100 nM concentrations of the drug, applied for 96 h, lead to a highly significant decrease in the viable cell number (p < 0. 001). A mean reduction of the viable cell number between 30% and 40% (60% and 90%) was observed for a drug concentration of 10nM (100nM). A round cell morphology occured in most EPO treated cells and the organized network of microtubules was shrunk in these round cells. The tubulin immunostaining now appeared amorphous and was restricted to small perinuclear regions. Large actin filaments also disappeared, but actin staining was present in the whole cytosplasm. These results prove that EPOs have antiproliferative effects in glioma cells and affect their tubulin cytoskeleton, as it was previously observed in several types of carcinoma cells.
KW - Actin
KW - Epo-D epothilone
KW - Glioblastoma
KW - Microtubules
KW - MTT assay
UR - http://www.scopus.com/inward/record.url?scp=0348135043&partnerID=8YFLogxK
U2 - 10.1023/B:NEON.0000003679.40609.63
DO - 10.1023/B:NEON.0000003679.40609.63
M3 - Article
C2 - 14686728
AN - SCOPUS:0348135043
SN - 0167-594X
VL - 65
SP - 99
EP - 106
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 2
ER -