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Costunolide Triggers Apoptosis in Human Leukemia U937 Cells by Depleting Intracellular Thiols
Choi, Jung-Hye,Ha, Joohun,Park, Jae-Hoon,Lee, Jae Yeol,Lee, Yong Sup,Park, Hee-Juhn,Choi, Jong-Won,Masuda, Yutaka,Nakaya, Kazuyasu,Lee, Kyung-Tae WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2002 東西醫學硏究所 論文集 Vol.2002 No.-
We have preciously 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 costunlide induces apoptosis in human promonocytic leukemia U937 cells by depleting the intracellular thiols. Cos-tunolide treatment rapidly depleted the intracellular reduced glutathione (GSH) and protein thiols, and this prereded the ocrurrence of apoptosis. Pretreatment with sulfhydryl compounds such as GSH, N-acetyl-L-cysteline, dithiothreitol and 2-mercaptoethanol almost completely blocked the costunolide-induced apoptosis, highlighting the significance of the intracellular thiol level in the Process. Furthermore, overexpression or 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 intracellu1ar thiols contents, which are modulated by Bcl-2.