Costunolide Induces Apoptosis via Modulation of Cyclin-Dependent Kinase in HL-60 Human Leukemia Cells

被引:4
|
作者
Kim, Dong Hee [2 ]
Choi, Jung-Hye [3 ]
Park, Hee-Juhn [4 ]
Park, Jae-Hoon [5 ]
Lee, Kyung-Tae [1 ]
机构
[1] Kyung Hee Univ, Coll Pharm, Dept Biochem, Seoul 130701, South Korea
[2] KonKuk Univ, Sch Med, Chungju Hosp, Dept Ophthalmol, Chungju 380704, South Korea
[3] Kyung Hee Univ, Coll Pharm, Dept Oriental Pharmaceut Sci, Seoul 130701, South Korea
[4] Sangji Univ, Dept Pharmaceut Engn, Wonju 220702, South Korea
[5] KonKuk Univ, Sch Med, Chungju Hosp, Dept Ophthalmol, Chungju 380704, South Korea
关键词
Costunolide; Apoptosis; Cdc2; Leukemia cell; GENE-EXPRESSION; ACTIVATION; MECHANISM; DEATH; BAX;
D O I
10.4062/biomolther.2010.18.2.178
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
Costunolide is an active compound isolated from the stem bark of Magnolia sieboldii, and is considered a potential therapeutic for the treatment of various cancers. In this study, we investigated the underlying mechanism whereby costunolide induces the apoptosis of human leukemia cells. Using apoptosis analysis and quantitative reverse transcription-polymerase chain reaction (RT-PCR) results obtained during this study show that costunolide is a potent inducer of apoptosis and that it is triggered due to the premature activation of Cdc2. G(1)-synchronized cells, which cannot undergo mitosis, were found to be more sensitive to costunolide, and Cdc2 mRNA levels were increased by costunolide treatment. Furthermore, the Cdk inhibitors, olomucine and butyrolactone I, were found to suppress costunolide-induced apoptosis. In addition, the PKC activator TPA rescued cells from cell death by costunolide, and this was prevented by the PKC inhibitor staurosporin. The present study suggests that costunolide induces the apoptosis of HL-60 leukemic cells by modulating cyclin-dependent kinase Cdc2.
引用
收藏
页码:178 / 183
页数:6
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