Induction of enantio-selective apoptosis in human leukemia HL-60 cells by (S)-erypoegin K, an isoflavone isolated from Erythrina poeppigiana
Induction of enantio-selective apoptosis in human leukemia HL-60 cells by (S)-erypoegin K, an isoflavone isolated from Erythrina poeppigiana
复制标题
DOI：
10.1016/j.bmc.2020.115490
复制
发表时间：
2020-06-01
影响因子：
3.5
通讯作者：
Kaneda, Norio
中科院分区：
文献类型：
--
作者：
Hikita, Kiyomi;Saigusa, Satomi;Kaneda, Norio
Erypoegin K是从刺五加树皮中分离得到的一种异黄酮类化合物，对人白血病HL-60细胞具有很强的诱导凋亡作用。Erypoegin K在呋喃环的C-2‘’位置有一个手性碳，自然地以(S)和(R)-异构体的外消旋混合物的形式存在。在本研究中，我们从金雀异黄素中半合成了(RS)-erpoegin K，并利用手性柱分离光学异构体，以表征其诱导细胞凋亡的活性。通过分析caspase-3和caspase-9的激活、核碎裂和基因组DNA梯带形成来评估细胞的凋亡性。(S)-Elepoegin K具有独特的抗增殖和诱导凋亡活性，其IC50值为90 nM，比其外消旋混合物的IC50值(175 NM)低约50%。相反，(R)-异构体没有表现出诱导细胞凋亡的活性。此外，只有在(S)-Elepoegin K处理的细胞中才观察到甲基乙二醛的积累。这些结果表明，(S)-Elepoegin K是一种独特的生物活性成分，对HL-60细胞具有很强的诱导凋亡活性。
Erypoegin K, an isoflavone isolated from the stem bark of Erythrina poeppigiana, has potent apoptosis-inducing effect on human leukemia HL-60 cells. Erypoegin K has a chiral carbon at the C-2 '' position of its furan ring and naturally occurs as a racemic mixture of (S)- and (R)-isomers. In the present study, we semi-synthesized (RS)-erypoegin K from genistein and separated the optical isomers by HPLC using a chiral column to characterize its apoptosis-inducing activity. Apoptotic cell death was assessed by analyzing caspase-3 and caspase-9 activation, nuclear fragmentation, and genomic DNA ladder formation. (S)-erypoegin K showed exclusive anti-proliferative and apoptosis-inducing activity, with an IC50 value of 90 nM, about 50% lower than that of its racemic mixture (175 nM). By contrast, no apoptosis-inducing activity was shown by the (R)-isomer. In addition, methylglyoxal accumulation in the culture medium was observed only in cells treated with (S)-erypoegin K. These results demonstrated that (S)-erypoegin K is a unique bioactive component that has potent apoptosis-inducing activity on HL-60 cells.