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Costunolide triggers apoptosis in human leukemia U937 cells by depleting intracellular thiols.

Authors
  • Choi, Jung-Hye1
  • Ha, Joohun
  • Park, Jae-Hoon
  • Lee, Jae Yeol
  • Lee, Yong Sup
  • Park, Hee-Juhn
  • Choi, Jong-Won
  • Masuda, Yutaka
  • Nakaya, Kazuyasu
  • Lee, Kyung-Tae
  • 1 College of Pharmacy, Kyung-Hee University, Hoegi-Dong, Dongdaemun-Ku, Seoul 130-701, Korea. , (North Korea)
Type
Published Article
Journal
Japanese journal of cancer research : Gann
Publication Date
December 2002
Volume
93
Issue
12
Pages
1327–1333
Identifiers
PMID: 12495472
Source
Medline
License
Unknown

Abstract

We have previously demonstrated that costunolide, a biologically active compound that was isolated from the stem bark of Magnolia sieboldii, induced apoptosis in human cancer cells. In the present study, we investigated the underlying mechanisms and suggest that costunolide induces apoptosis in human promonocytic leukemia U937 cells by depleting the intracellular thiols. Costunolide treatment rapidly depleted the intracellular reduced glutathione (GSH) and protein thiols, and this preceded the occurrence of apoptosis. Pretreatment with sulfhydryl compounds such as GSH, N-acetyl-L-cysteine, dithiothreitol and 2-mercaptoethanol almost completely blocked the costunolide-induced apoptosis, highlighting the significance of the intracellular thiol level in the process. Furthermore, overexpression of Bcl-2 also significantly attenuated the effects of costunolide. The apoptosis-inducing activity of costunolide is likely to depend on the exomethylene moiety because derivatives in which this group was reduced, such as dihydrocostunolide and saussurea lactone, did not deplete the cellular thiols and showed no apoptotic activity. Taken together, the present study demonstrates that the costunolide-induced apoptosis depends on intracellular thiols contents, which are modulated by Bcl-2.

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