Sesquiterpenoids from the roots of Inula helenium inhibit acute myelogenous leukemia progenitor cells

被引:15
作者
Ding, Yahui [1 ,2 ]
Pan, Wenwei [1 ,2 ]
Xu, Junqing [3 ]
Wang, Tianpeng [1 ,2 ]
Chen, Tianyang [1 ,2 ]
Liu, Zhongquan [1 ,2 ]
Xie, Chunfeng [1 ,2 ]
Zhang, Quan [1 ,2 ]
机构
[1] Nankai Univ, Coll Pharm, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China
[2] Nankai Univ, Tianjin Key Lab Mol Drug Res, Tianjin 300071, Peoples R China
[3] Qingdao Univ, Yantai Yuhuangding Hosp, Dept Hematol, Med Coll, Yantai 264000, Peoples R China
基金
中国国家自然科学基金;
关键词
Inula helenium; Sesquiterpenes; Human leukemia stem-like cell line; Apoptosis; Mitochondria-dependent pathway; LACTONES; STEM; EUDESMANOLIDES;
D O I
10.1016/j.bioorg.2019.01.055
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A One new eudesmane sesquiterpenoid, 11 beta-hydroxy-13-chloro-eudesm-5-en-12, 8-olide (1), was isolated from the roots of Inula helenium together with nine eudesmanolides (2-10) and one germacranolide (11). Their structures were elucidated on the basis of detailed spectroscopic analyses. All isolates were evaluated for their anti-proliferative activities against human leukemia stem-like cell line KG1a. Compound 10 exhibited the most potent effect with the IC50 value of 3.36 +/- 0.18 mu M. A further investigation revealed that compound 10 could significantly induce apoptosis of KG1a cells. Additionally, compound 10 had an obvious effect on the levels of apoptosis-related proteins (Bcl-2, Bax, cytochrome c, caspase 9 and caspase 3), indicating that the anti-proliferative effect of compound 10 on KG1a cells might be mediated through a mitochondria-dependent apoptotic pathway.
引用
收藏
页码:363 / 367
页数:5
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