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 successive phytochemical isolation from Magnolia sieboldii (Magnoliaceae), a novel acyclic monoterpene 1 named deoxygeraniol [2,6(E)-dimethyl-2,6-octadiene] was isolated along with beta-sitosterol 3-O-linoleate (2), trilinolein (3) and high amount of costunolide (4) in the pure state. The structure of compound 1 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
Park
H J
HJ
Division of Applied Plant Science, Sang-ji University, Wonju, Korea.
Kwon
S H
SH
Han
Y N
YN
Choi
J W
JW
Miyamoto
K
K
Lee
S H
SH
Lee
K T
KT
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D053938:DNA Fragmentation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D006868:Hydrolysis; D029562:Magnoliaceae / Q000737:chemistry*; D051379:Mice; D019441:Plant Epidermis / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D013729:Terpenes / Q000302:isolation & purification / Q000494:pharmacology*; D007783:Lactones
D000111:Acetylcysteine; D020169:Caspases; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D011065:Poly(ADP-ribose) Polymerases; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D013729:Terpenes; C002602:costunolide; D007783:Lactones