Norcantharidin induces human melanoma A375-S2 cell apoptosis through mitochondrial and caspase pathways.
Norcantharidin induces human melanoma A375-S2 cell apoptosis through mitochondrial and caspase pathways.
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DOI：
10.3346/jkms.2004.19.4.560
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发表时间：
2004-08
影响因子：
4.5
通讯作者：
Ikejima T
中科院分区：
文献类型：
--
作者：
An WW;Wang MW;Tashiro S;Onodera S;Ikejima T
去甲斑泻素(Norcantharidin，NCTD)是斑泻素的去甲基化形式，是斑羚的活性物质。为探讨NCTD诱导A375-S2细胞死亡的途径，采用了3-(4，5-二甲基噻唑-2-基)-2，5-二苯基四氮唑溴化法、光学显微镜观察、DNA琼脂糖凝胶电泳、半胱氨酸天冬氨酸氨基转移酶活性测定和Western印迹分析等方法。经NCTD处理的A375-S2细胞呈现典型的细胞凋亡特征。NCTD对人黑色素瘤A375-S2细胞的抑制作用可被caspase抑制剂caspase-3和caspase-9部分逆转。NCTD处理后不同时间caspase-3、-9活性均显著升高。半胱氨酸氨基转移酶激活的DNA酶抑制物的表达呈时间依赖性降低，同时，Bcl2/Bax或Bclxl/Bax的比值降低，并可被Caspase-3抑制剂逆转。NCTD诱导A375-S2细胞凋亡过程中，胞浆细胞色素c表达增加，caspase-3抑制剂对细胞色素c表达上调无明显影响，提示NCTD诱导A375-S2细胞凋亡，caspase激活和线粒体途径参与了细胞凋亡过程。
Norcantharidin (NCTD) is the demethylated form of cantharidin, which is the active substance of mylabris. To examine the pathway of NCTD-induced A375-S2 cell death, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheyltetrazolium bromide (MTT) assay, photomicroscopical observation, DNA agarose gel electrophoresis, caspase activity assay and Western blot analysis were carried out. A375-S2 cells treated with NCTD exhibited several typical characteristics of apoptosis. The inhibitory effect of NCTD on human melanoma, A375-S2 cells, was partially reversed by the inhibitors of pan-caspase, caspase-3 and caspase-9. The activities of caspase-3 and -9 were significantly increased after treatment with NCTD at different time. The expression of inhibitor of caspase-activated DNase was decreased in a time-dependent manner, simultaneously, the ratio of Bcl-2/Bax or Bcl-xL/Bax was decreased and the expression ratio of proteins could be reversed by caspase-3 inhibitor. The expression of cytochrome c in cytosol was increased after NCTD treatment and caspase-3 inhibitor had no significant effect on the up-regulation of cytochrom c. These results suggest that NCTD induced A375-S2 cell apoptosis and the activation of caspase and mitochondrial pathway were involved in the process of NCTD-induced A375-S2 cell apoptosis.
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作者：
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