Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Costunolide Induces Apoptosis via Modulation of Cyclin-Dependent Kinase in HL-60 Human Leukemia Cells

  • Kim, Dong-Hee (Department of Ophthalmology, Chungju Hospital, KonKuk University School of Medicine) ;
  • Choi, Jung-Hye (Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Park, Hee-Juhn (Department of Pharmaceutical Engineering, Sangji University) ;
  • Park, Jae-Hoon (Department of Pathology, College of Medicine, Kyung Hee University) ;
  • Lee, Kyung-Tae (Department of Biochemistry, College of Pharmacy, Kyung Hee University)
  • Received : 2010.04.13
  • Accepted : 2010.04.22
  • Published : 2010.04.30
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Abstract

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.

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References

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