Planta Med 2001; 67(4): 358-359
DOI: 10.1055/s-2001-14315
Letters

© Georg Thieme Verlag Stuttgart · New York

Costunolide, a Sesquiterpene from the Stem Bark of Magnolia sieboldii, Inhibits the RAS-Farnesyl-Proteintransferase

Sung-Hee Park1 , Sang-Un Choi1 , Chong Ock Lee1 , Sung-eun Yoo1 , Seok Keun Yoon1 , Young-Kyoon Kim2 , Shi Yong Ryu1,*
  • 1 Korea Research Institute of Chemical Technology, Taejeon, Korea
  • 2 College of Forest Science, Kookmin University, Seoul, Korea
Further Information

Publication History

June 2, 2000

August 19, 2000

Publication Date:
31 December 2001 (online)

Abstract

Costunolide, a germacrane sesquiterpene lactone isolated from the stem bark of Magnolia sieboldii demonstrated a significant inhibition upon the farnesylation process of human lamin-B by farnesyl-proteintransferase (FPTase), in a dose dependent manner in vitro (IC50 value was calculated as 20 μM). It was also found to exhibit an inhibition upon the proliferation of cultured human tumor cells, i.e., A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon), in vitro.

References

  • 1 Kohl N E, Mosser S D, deSolms S J, Giuliani E A, Pompliano D L, Graham S L et al. Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor.  Science. 1993;  260 1934-7
  • 2 Sepp-Lorenzino L, Ma Z, Rands E, Kohl N E, Gibbs J B, Oliff A et al. Peptidomimetic inhibitor of farnesyl:protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines.  Cancer Res.. 1995;  55 5302-9
  • 3 Jayasuriya H, Silverman K C, Zink D L, Jenkins R G, Sanchez M, Pelaez F et al. Clavaric acid: A triterpenoid inhibitor of farnesyl-protein transferase from Clavariadelphus truncatus .  J. Nat. Prod.. 1998;  61 1568-70
  • 4 Singh S B, Zink D L, Liesch J M, Goetz M A, Jenkins R G, Nallin-Omstead M et al. Isolation and structure of chaetomellic acid A and B from Chaetomella acustiseta: Farnesyl pyrophosphate mimics inhibitors of Ras farnesyl-protein transferase.  Tetrahedron. 1993;  49 5917-26
  • 5 Skehan P, Streng R, Scudiero D, Monks A, McMahon J, Vistica D et al. New colorimetric cytotoxicity assay for anticancer-drug screening.  J. Natl. Cancer. Inst.. 1990;  82 1107-12
  • 6 Mori H, Kawamori T, Tanaka T, Ohnishi M, Yamahara J. Chemopreventive effect of costunolide, a constituent of Oriental medicine, on azoxymethane-induced intestinal carcinogenesis in rats.  Cancer lett.. 1994;  83 171-5
  • 7 Mondranondra I O, Che C T, Rimando A M, Vajrodaya S, Fong H H, Farnsworth N R. Sesquiterpene lactones and other constituents from a cytotoxic extract of Michelia floribunda .  Pharm. Res.. 1990;  7 1269-72
  • 8 Park H J, Jung W T, Basnet P, Kadota S, Namba T. Syrigin 4-O-glucoside, a new phenylpropanoid glycoside, and costunolide, a nitric oxide synthase inhibitor, from the stem bark of Magnolia sieboldii .  J. Nat. Prod.. 1996;  59 1128-30
  • 9 Chen H C, Chou C K, Lee S D, Wang J C, Yeh S F. Active compounds from Saussurea lappa Clarks that suppress hepatitis B virus surface antigen gene expression in human hepatoma cells.  Antiviral Res.. 1995;  27 99-109
  • 10 Somasekar R A, Kelkar G R, Bhattacharyya S C. The structure of costunolide, a new sesquiterpene lactone from coctus root oil.  Tetrahedron. 1960;  9 275-83
  • 11 Reiss Y, Goldstein J L, Seabra M C, Casey P J, Brown M S. Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides.  Cell. 1990;  62 81-8
  • 12 Reiss Y, Seabra M C, Armstrong S A, Slaughter C A, Goldstein J L, Brown M S. Nonidentical subunits of p21H-ras farnesyltransferase.  J. Biol. Chem.. 1991;  266 10672-7

Dr. Shi Yong Ryu

Korea Research Institute of Chemical Technology

Yusung P.O. Box 107

Taejeon

Korea 305-606

Email: syryu@pado.krict.re.kr

Fax: +82-42-861-1291

Phone: +82-42-860-7163