Apoptosis-inducing costunolide and a novel acyclic monoterpene from the stem bark of Magnolia sieboldii

In a course of obtaining more amount of bioactive costunolide and successiv e phytochemical isolation from Magnolia sieboldii (Magnoliaceae), a novel a cyclic monoterpene 1 named deoxygeraniol {2,6(E)-dimethyl-2,6-octadiene} wa s isolated along with beta -sitosterol 3-O-linoleate (2), trilinolein (3) a nd high amount of costunolide (4) in the pure state. The structure of compo und 1 was determined on the basis of spectroscopic data. Costunolide was fo und to induce apoptotic cell death in a dose-dependent manner by nucleosoma l 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 cyt otoxicity. These results suggest that costunolide-induced cell death is med iated by reactive oxygen species.