Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells.
Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells.
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复合K是人参皂苷的代谢产物，通过HL-60人白血病细胞中的caspase-8依赖性途径诱导凋亡。
DOI：
10.1186/1471-2407-9-449
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发表时间：
2009-12-18
期刊：
影响因子：
3.8
通讯作者：
Lee KT
中科院分区：
文献类型：
--
作者：
Cho SH;Chung KS;Choi JH;Kim DH;Lee KT
化合物K-[20-O-β-(D-glucopyranosyl)-20(S)-protopanaxadiol]，是人参中原人参二醇型皂苷的代谢产物，具有抗肿瘤、抑制血管生成和诱导肿瘤细胞凋亡的作用。在本研究中，我们研究了化合物K对HL-60细胞凋亡的影响，并探讨了其可能的作用机制。我们用四甲基偶氮唑盐比色法检测了化合物K对不同癌细胞系存活率的影响。采用DAPI比色法、Annexin V和PI双染法、Western印迹法和免疫沉淀法检测化合物K诱导细胞凋亡的作用。化合物K以剂量和时间依赖的方式抑制HL-60细胞的存活，其IC50值为14μM。此外，这种细胞死亡具有典型的细胞凋亡特征，即DNA片段化、DNA梯形形成和以Annexin V为靶点的磷脂酰丝氨酸残基在HL-60细胞中外化。此外，化合物K诱导了一系列与线粒体和死亡受体依赖的细胞凋亡途径相关的细胞内事件，即：(1)caspase-3、-8和-9的激活；(2)线粒体膜电位的丧失；(3)细胞色素c和Smac/Diablo释放到胞浆；(4)Bid和Bax移位到线粒体；(5)下调Bcl2和BclxL的表达。此外，caspase-8抑制剂完全阻断了化合物K对caspase-3的激活、Bid裂解和随后的DNA断裂。有趣的是，放线菌酮可显著阻止caspase-3和-8的激活以及DNA的断裂，提示化合物K诱导的细胞凋亡依赖于从头蛋白的合成。结果表明，caspase-8通过Bid裂解、细胞色素c的释放和caspase-9的激活直接或间接地激活caspase-3，在化合物K诱导的细胞凋亡中起关键作用。
Compound K [20-O-β-(D-glucopyranosyl)-20(S)-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells. We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis. Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1) the activation of caspases-3, -8, and -9; (2) the loss of mitochondrial membrane potential; (3) the release of cytochrome c and Smac/DIABLO to the cytosol; (4) the translocation of Bid and Bax to mitochondria; and (5) the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis. The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation.
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影响因子：
2.7
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