Subscribe to RSS
DOI: 10.1055/s-2003-38879
Two Cytotoxic Sesquiterpene Lactones from the Leaves of Xanthium strumarium and their in vitro Inhibitory Activity on Farnesyltransferase
Publication History
Received: July 1, 2002
Accepted: November 7, 2002
Publication Date:
23 April 2003 (online)
Abstract
Two xanthanolide sesquiterpene lactones, 8-epi-xanthatin (1) and 8-epi-xanthatin epoxide (2), isolated from the leaves of Xanthium strumarium (Compositae), demonstrated a significant inhibition on the proliferation of cultured human tumor cells, i. e., A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nervous system) and HCT-15 (colon) in vitro. They were also found to inhibit the farnesylation process of human lamin-B by farnesyltransferase (FTase), in a dose-dependent manner in vitro (IC50 value was calculated as 64 and 58 μM, respectively). Due to the relatively high concentrations of 1 and 2 required to obtain an FTase inhibition as compared with those necessary for a cytotoxic effect on tumor cells, it remains unclear whether a relationship between these two activities exists.
References
- 1 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
- 2 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
- 3 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
- 4 Jayasuriya H, Silverman K C, Zink D L, Jenkins R , 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
- 5 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 mimic inhibitors of Ras farnesyl-protein transferase. Tetrahedron. 1993; 49 5917-26
- 6 Park S H, Choi S U, Lee C O, Yoo S, Yoon S K, Kim Y K, Ryu S Y. Costunolide, a sesquiterpene from the stem bark of Magnolia sieboldii, inhibits the Ras-farnesyl-protein transferase. Planta Medica. 2001; 67 358-9
- 7 Shaikenov T E, Adekenov S M, Williams R M, Prashad N, Baker F L, Madden T L, Newman R. Arglabin-DMA, a plant derived sesquiterpene inhibits farnesyltransferase. Oncol Rep. 2001; 8 173-9
- 8 Sato Y, Oketani H, Yamada T, Singyouchi K, Ohtsubo T, Kihara M. et al . A xanthanolide with potent antibacterial activity against methicillin-resistant Staphylococcus aureus . J Pharm Pharmacol. 1997; 49 1042-4
- 9 Roussakis C, Chinou I, Vayas C, Harvala C, Verbist J F. Cytotoxic activity of xanthatin and the crude extracts of Xanthium strumarium . Planta Medica. 1994; 60 473-4
- 10 Lee H J, Jeong Y S, Ryu S Y, Ryu J H. Inhibition of nitric oxide synthesis by 8-epi-xanthatin inactivated RAW 264.7 cells. Yakhak Hoeji. 1998; 42 540-3
- 11 Bohlmann F, Singh P, Joshi K C, Singh C L. Xanthanolide from Xanthium indicum . Phytochemistry.. 1982; 21 1441-3
- 12 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
- 13 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 10 672-7
Dr. Shi Yong Ryu
Korea Research Institute of Chemical Technology
Yusung P.O. Box 107
Taejeon
Korea 305-606
Phone: +82-42-860-7163
Fax: +82-42-860-7160
Email: syryu@krict.re.kr