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

Sung-Hee Park; Sang-Un Choi; Chong Ock Lee; Sung-eun Yoo; Seok Keun Yoon; Young-Kyoon Kim; Shi Yong Ryu

doi:10.1055/s-2001-14315

Planta Medica, Table of Contents

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

Letters

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 Ryu^1,*

¹ Korea Research Institute of Chemical Technology, Taejeon, Korea
² College of Forest Science, Kookmin University, Seoul, Korea

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.

Full Text

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