Induction of apoptosis by isoflavonoids from the leaves of Millettia taiwaniana in human leukemia HL-60 cells
Induction of apoptosis by isoflavonoids from the leaves of Millettia taiwaniana in human leukemia HL-60 cells
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DOI：
10.1055/s-2005-916259
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发表时间：
2006-04-01
期刊：
影响因子：
2.7
通讯作者：
Furukawa, H
中科院分区：
文献类型：
--
作者：
Ito, C;Murata, T;Furukawa, H
我们从台湾崖豆藤（Millettia taiwaniana Hayata）叶中分离出两个新的生物碱类化合物：millewanin-F（1）和furowanin-A（2），以及五个已知的生物碱类化合物，并研究了它们对人白血病HL-60细胞生长的影响。在分离的甘草酸中，糠蛙素-A（2）、瓦兰酮（3）、异异赤藓烯galensein-E（4）和丁香酮B（10）（6）对HL-60细胞显示出显著的细胞毒性。在用三种细胞毒性抑制剂furowanin-A（2）、warangalone（3）和isoerysenegalensein-E（4）处理后，Hoechst 33342染色的荧光显微镜显示，细胞核碎裂和染色质浓缩的凋亡细胞百分比以时间依赖性方式增加。另外，在用天冬氨酸2、3和4处理后，半胱天冬酶-9和半胱天冬酶-3的活性也以时间依赖性方式增强。半胱天冬酶-9和半胱天冬酶-3抑制剂抑制由天冬氨酸2、3和4诱导的细胞凋亡。这些结果表明，在HL-60细胞中，顺铂通过激活caspase-9/caspase-3途径诱导凋亡，这是由线粒体功能障碍触发的。
We have isolated two new isoflavonoids, millewanin-F (1) and furowanin-A (2), together with five known isoflavonoids from the leaves of Millettia taiwaniana Hayata (Leguminosae) and examined their effects on the growth of human leukemia HL-60 cells. Among the isolated isoflavonoids, furowanin-A (2), warangalone (3), isoerysenegalensein-E (4), and euchrenone b(10) (6) showed significant cytotoxicity against HL-60 cells. After treatment with three of the cytotoxic isoflavonoids, furowanin-A (2), warangalone (3), and isoerysenegalensein-E (4), fluorescence microscopy with Hoechst 33342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin increased in a time-dependent manner. in addition, the activities of caspase-9 and caspase-3 were also enhanced in a time-dependent manner upon treatment with the isoflavonoids 2, 3, and 4. Caspase-9 and caspase-3 inhibitors suppressed apoptosis induced by isoflavonoids 2, 3, and 4. These results suggest that the isoflavonoids induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, which is triggered by mitochondrial dysfunction.