Induction of apoptosis by carbazole alkaloids isolated from Murraya koenigii
Induction of apoptosis by carbazole alkaloids isolated from Murraya koenigii
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DOI：
10.1016/j.phymed.2005.03.010
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发表时间：
2006-05-01
期刊：
影响因子：
7.9
通讯作者：
Furukawa, H
中科院分区：
文献类型：
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作者：
Ito, C;Itoigawa, M;Furukawa, H
本研究从芸香科Murraya koenigii植物中分离出10种咔唑类生物碱，研究了它们对人白血病HL-60细胞生长的影响。三种咔唑类生物碱，马汉碱(6),pyrayafoline-D(7)和murrafoline-I(9)对HL-60细胞表现出显著的细胞毒性。荧光显微镜Hoechst 33342染色显示，每一种生物碱处理后，细胞核碎片化和染色质浓缩的凋亡细胞百分比呈时间依赖性增加。有趣的是，每一种咔唑生物碱都引起线粒体膜电位的丧失。此外，caspase-9和caspase-3在生物碱作用下也具有时间依赖性。Caspase-9和caspase-3抑制剂可抑制这些生物碱诱导的细胞凋亡。结果表明，这三种生物碱通过激活caspase-9/caspase-3通路，通过线粒体功能障碍诱导HL-60细胞凋亡。(c) 2005 Elsevier GmbH版权所有。
In the current study, we isolated 10 carbazole alkaloids from the plant species Murraya koenigii (Rutaceae), and examined their effects on the growth of the human leukemia cell line HL-60. Three carbazole alkaloids, mahanine (6), pyrayafoline-D (7) and murrafoline-I (9), showed significant cytotoxicity against HL-60 cells. Fluorescence microscopy with Hoechst 33342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin was increased in a time-dependent manner after treatment with each alkaloid. Interestingly, each carbazole alkaloid induced the loss of mitochondrial membrane potential. In addition, both caspase-9 and caspase-3 were also time-dependently activated upon treatment with the alkaloids. Caspase-9 and caspase-3 inhibitors suppressed apoptosis induced by these alkaloids. The results suggest that these three alkaloids induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, through mitochondrial dysfunction. (c) 2005 Elsevier GmbH. All rights reserved.