Apoptosis-Inducing Costunolide and a Novel Acyclic Monoterpene from the Stem Bark of Magnolia sieboldii

  • Published : 2001.08.01

Abstract

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.

Keywords

References

  1. Handbook of Natural Products Data Ahmad V.U;Att-ur-Rahman
  2. Planta Medica v.58 A new dehydroeugenol from Magnolia officinalis Baek,N.I.;Kim,H.;Lee,Y.U.;Park,J.D.;Kang,K.S.;Kim,S.I.
  3. Surgical oncology v.6 Apoptosis, cancer and cancer therapy Bold,R.J.;Termuhlen,P.M.;McConkey,D.J.
  4. Chem. Pharm. Bull. v.36 Three new neolignans, fargesones A, B and C, from the flower buds of Magnolia fargesii Chen,C.C.;Huang,Y.L.;Chen,Y.P.;Hsu,H.Y.;Kuo,Y.H.
  5. Planta Medica v.64 Inhibitory effect of sesquiterpene lactones from Saussurea on tumor-necrosis factor-α production in murine macrophage-like cells Cho,J.Y.;Park,J.S.;Yoo,E.S.;Baik,K.U.;Jung,J.H.;Lee,J.S.;Park,M.H.
  6. Leukemia v.13 Cleavage of Bcl-2 is an early event in chemotherapy-induced apoptosis of human myeloid leukemia cells Fadeel,B.;Hassan,Z.;Hellstrom Lindberg,E.;Henter,J.I.;Orrenius,S.;Zhivotovsky,B.
  7. Biochem. Biophys. Res. Commun. v.204 Antioxidant, gallic acid, induces apoptosis in HL-60RG cells Inoue,M.;Suzuki,R.;Koide,T.;Sakaguchi,N.;Ogihara,Y.;Yabu,Y.
  8. Int. J. Hematol. v.68 Mechanism involved in chemotherapy-induced apoptosis and their implications in cancer chemotherapy Kamesaki,H.
  9. Planta Medica v.60 Anti-emetic principles of Magnolia obovata Bark and Zinger officinale rhizome Kawai,T.;Kinoshita,K.;Koyama,K.;Takahashi,K.
  10. Planta Medica v.51 Anti-inflammatory effect of neolignans newly isolated from the crude drug Shin-l (Flos Magnoliae) Kimura,M.;Suzuki,J.;Yamada,T.;Yoshizaki,M.;Kikuchi,T.;Kadota,S.;Matsuda,S.
  11. Biol. Pharm. Bull. v.23 Role of reactive oxygen species in the regulation of physiological functions Kiyoshi,N.
  12. Biochim. Biophys. Acta. v.1317 Curcumin, an anti-oxidant and anti-tumor promoter, induces apoptosis in human leukemia cells Kuo,M.L.;Huang,T.S.;Lin,J.K.
  13. Planta Medica v.65 A sesquiterpene, dehydrocostus lactone, inhibits the expression of inducible nitric oxide synthase and TNF-α in LPS-activated macrophages Lee,H.J.;Kim,N.Y.;Jang,H.J.;Kim,K.M.;Sohn,D.H.;Lee,S.H.;Ryu,J.H.
  14. Planta Medica v.66 Essential moiety for antimutagenic and cytotoxic activity of hederagenin monodesmosides and bisdesmosides isolated from the stem bark of Kalopanax pictus Lee,K.T.;Sohn,I.C.;Park,H.J.;Kim,D.W.;Jung,G.O.;Park,K.Y.
  15. J. Org. Chem. v.47 Palladium-catalyzed reactions of allylic electrophiles with organomettalic reagents. A regioselective 1,4-elimination and a regio-and stereoseletive reduction of allylic derivatives Matsushita,H.;Neigishi,E.
  16. Planta Medica v.44 Dental caries prevention by traditional Chinese medicines Namba,T.;Tsunezuka,M.;Hattori,M.
  17. J. Nat. Prod. v.59 Syringin 4-O-β-glucoside, a new phenylpropanoid glycoside, and costunolide, a nitric oxide synthase inhibitor, from the stem bark of Magnolia sieboldii Park,H.J.;Jung,W.T.;Basnet,P.;Kadota,S.;Namba,T.
  18. Phytochemistry v.21 15-acetoxycostunolide from Magnolia sieboldii Taba,H.;Fujioka,R.;Takayama,Y.
  19. Biochem. Biophys. Res. Commun. v.230 Involvement of cellular proteolytic machinery in apoptosis Zhivotovsky,B.;Burgess,D.H.;Vanags,D.M.;Orrenius,S.