Apoptosis-inducing Costunolide and a novel acyclic monoterpene from the stem bark ofMagnolia sieboldii

In a course of obtaining more amount of bioactive costunolide and successive phytochemical isolation fromMagnolia sieboldii (Magnoliaceae), a novel acyclic monoterpene 1 named deoxygeraniol (2,6(E)-dimethyl-2, 6-octadiene) was isolated along with β-sitosterol 3-O-linoleate (2), trilinolein (3) and high amount of costunolide (4) in the pure state. The structure of compound1 was determined on the basis of spectroscopic data. Costunolide was found to induce apoptotic cell death in a dose-dependent manner by nucleosomal DNA ladder and flow cytometric analysis. Immunoblot analysis showed that the level of the anti-apoptotic protein, Bcl-2, was decreased, whereas the cleavage of poly-(ADP-ribose) polymerase was activated. Furthermore, the N-acetyl-L-cysteine antioxidant effectively prevented costunolide-induced cytotoxicity. These results suggest that costunolide-induced cell death is mediated by reactive oxygen species Received March 20, 2001

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