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KMID : 0613820100200040519
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Journal of Life Science
2010 Volume.20 No. 4 p.519 ~ p.527
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Paclitaxel Induced Caspase-Independent Mitotic Catastrophe in Rabbit Articular Chondrocyte
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Im Jeong-Hee
Kim Song-Ja
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Abstract
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Paclitaxel is known as a potent inhibitor of microtubule depolymerization. It leads to mitotic arrest and cell death by stabilizing the spindle in various cell types. Here, we investigated the effects of paclitaxel on the proliferation and cell death of rabbit articular chondroeytes. Paclitaxel inhibited proliferation in a dose- and time- dependent manner, determined by MTT assay in rabbit articular chondrocytes. We also established paclitaxel-induced G2/M arrest by fluorescent activated cell sorter (FACS) analysis. Paclitaxel increased expression of cyclin B, p53 and p2l, while reducing expression of cdc2 and cdc25C in chondrocytes, as detected by Western blot analysis. Interestingly, paclitaxel showed the mitotic catastrophe that leads to abnormal nucleus division and cell death without DNA fragmentation through activation of caspase. Cell death by mitotic catastrophe in cells treated with paclitaxel was suppressed by inhibiting G1/S arrest with 2 mM thymidine. These results demonstrate that paclitaxel induces cell death via mitotic catastrophe without activation of casepase in rabbit articular chondrocytes.
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KEYWORD
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Caspase-3, chondrocyte, mitotic catastrophe, paclitaxel
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