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

Title
Costunolide triggers apoptosis in human leukemia U937 cells by depleting intracellular thiols.
Authors
최정혜하주훈박재훈이재열이용섭박희준최종훈Yutaka MasudaKazuyasu Nakaya이경태
Keywords
glutathione; Bcl-2; exomethylene; costunolide; apoptisis
Issue Date
2002-12
Publisher
Japanese Journal of Cancer Research
Citation
VOL 93, NO 12, 1327-1333
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.
URI
http://pubs.kist.re.kr/handle/201004/15974
ISSN
0910-5050
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KIST Publication > Article
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