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
