Open AccessCostunolide Triggers Apoptosis in Human Leukemia U937 Cells by Depleting Intracellular Thiols
Author(s) -
Choi JungHye,
Ha Joohun,
Park JaeHoon,
Lee Jae Yeol,
Lee Yong Sup,
Park HeeJuhn,
Choi JongWon,
Masuda Yutaka,
Nakaya Kazuyasu,
Lee KyungTae
Publication year - 2002
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2002.tb01241.x
Subject(s) - apoptosis , intracellular , u937 cell , dithiothreitol , glutathione , biochemistry , thiol , biology , cysteine , pharmacology , enzyme
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.