Mylabris phalerlata induces apoptosis by caspase activation following cytochrome c release and Bid cleavage
Mylabris phalerlata induces apoptosis by caspase activation following cytochrome c release and Bid cleavage
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DOI：
10.1016/s0024-3205(03)00568-x
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发表时间：
2003-09-12
期刊：
影响因子：
6.1
通讯作者：
Kim, SH
中科院分区：
文献类型：
--
作者：
Huh, JE;Kang, KS;Kim, SH
白蛉（Mylabris phalerata， MP）是一种在东方医学中用于治疗癌症的昆虫。在本研究中，我们检测了MP （BFMP）的丁醇（BuOH）部分，以确定其是否可以通过凋亡途径发挥抗癌活性，而毒性很小。发现BFMP对人单核白血病U937细胞（IC50 = 140马克杯/毫升）有特异性的细胞毒作用，而对外周血单核淋巴细胞（PBML, IC50 = 500马克杯/毫升以上）没有特异性的细胞毒作用。在31.25杯子/ml浓度下，BFMP还能诱导细胞凋亡的形态学改变，如染色质凝结、细胞收缩和DNA断裂等。此外，BFMP显著增加凋亡的annexin-V阳性细胞的比例呈剂量依赖性，并有效激活caspases（半胱氨酸天冬氨酸酶）级联，涉及caspases 8、9和3。BFMP还能有效地裂解Bcl-2家族的一种死亡激动剂Bid和聚（adp -核糖）聚合酶（PARP），并诱导随后细胞色素c从线粒体释放到细胞质中。但不影响Bcl-2和Bax的表达。综上所述，这些数据表明，黄皮草的BuOH提取物可以通过caspase级联激活和细胞色素c的释放诱导U937细胞凋亡，这是由Bid的产物诱导的。因此，我们认为BFMP具有抗癌活性，这种活性是通过细胞凋亡实现的，并且毒性很小。(C) 2003 Elsevier Inc.版权所有。
Mylabris phalerata (MP) is an insect that has been used for the treatment of cancer in oriental medicine. In the present study, the butanol (BuOH) fraction of MP (BFMP) was examined to determine whether it can exert anticancer activity through an apoptotic pathway with little toxicity. BFMP was found to have a specific cytotoxic effect on human monocytic leukemic U937 cells (IC50 = 140 mug/ml) rather than on peripheral blood mononuclear lymphocytes (PBML, IC50 = over 500 mug/ml). BFMP also induced the morphological changes of apoptosis, such as chromatin condensation, cell shrinking and DNA fragmentation at a concentration of 31.25 mug/ml. In addition, BFMP significantly increased the portion of apoptotic annexin-V positive cells in a dose-dependent manner, and effectively activated caspases (cysteine aspartase) cascade involving caspases 8, 9 and 3. BFMP also effectively cleaved Bid, a death agonist member of the Bcl-2 family and (poly(ADP-ribose)polymerase) (PARP) and induced the subsequent release of cytochrome c from mitochondria into the cytosol. However, it did not affect Bcl-2 and Bax expression. Taken together, these data suggest that the BuOH extract of Mylabris phalerata can induce apoptosis in U937 cells by caspase cascade activation in conjunction with cytochrome c release, induced by a product of Bid. Therefore, we conclude that BFMP has anti-cancer activity, which is achieved through apoptosis and is associated with little toxicity. (C) 2003 Elsevier Inc. All rights reserved.