Browse > Article

Screening of Inhibitory Activity of Plant Extracts against Farnesyl Protein Transferase  

Kang, Hyun-Mi (Korea Research Institute of Bioscience & Biotechnology)
Lee, Seung-Ho (Korea Research Institute of Bioscience & Biotechnology)
Ryu, Shi-Yong (Korea Research Institute of Chemical Technology)
Son, Kwang-Hee (Korea Research Institute of Bioscience & Biotechnology)
Yang, Deok-Cho (College of Natural Sciences, Chungbuk National University)
Kwon, Byoung-Mog (Korea Research Institute of Bioscience & Biotechnology)
Publication Information
Korean Journal of Pharmacognosy / v.34, no.1, 2003 , pp. 91-99 More about this Journal
Abstract
Ras proteins play an important role in intracellular signal transduction pathways involved in cell growth and the mutated twas genes have been found in thirty percent of human cancers. Ras proteins (H-, K- and N-Ras) are small guanine nucleotide binding proteins that undergo a series of posttranslational modifications including the farnesylation onto cysteine 186 at C-terminal of Ras by farnesyl protein transferase (FPTase). This is a mandatory process for retention of transforming ability. Therefore, inhibitors of FPTase have a promising to be effective antitumor agents. In our screening program for FPTase inhibitors, the methanol extracts of 193 plants were screened for the inhibitory activity against FPTase partially purified from the rat brain. Extracts of 7species plants including Areca catechu, Saururus chinensis, Curcuma longa, Artemisa princeps, Paeonia suffruticosa, Spatholobus suberectus, Cinnamomum cassia, Cinnamomum japonicum inhibited more than 60% of FPTase activity at a concentration of $100\;{\mu}g/ml$.
Keywords
Farnesyl protein transferase; Ras;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Hill, B.T., Perrin, D. and Kruczynski, A (2000) Inhibition of RAS-targeted prenylation: protein famesyl transerase inhibitors revisited Crit. Rev. Oncol. Hematol. 33: 7-23   DOI   ScienceOn
2 Sun, J., Qian, Y, Hamilton, A. D. and Sebti, S. M. (1995) Ras caaX peptidomimetic FTI 276 selectively blocks tumor growth in nude mice of a human lung carcinoma with k-ras mutation and p53 deletion. Caancer Res. 55: 4243-4247
3 Lee, S. H., Kim, M. J., Bok, S. H., Lee, H., Kwon, B. M., Shin, J. and Seo, Y. (1998) Arteminolide, an inhibitor of famesyl transferase from Artemisia sylvatica. J. Org. Chem. 63: 7111-7113   DOI   ScienceOn
4 Kohl, N. E., Mosser, S. D., DeSolms, S. J., Giuliani, E. A, Pompliano, D. L., Graham, S. L., Smith, R. L., Scolnick, E. M., Oliff, A and Gibbs, J. B. (1993) Selective inhibition of ras-dependent transformation by a famesyltransferase inhibitor. Science 260: 1934-1937   DOI   PUBMED
5 Singh, S.B., Zink, D.L., Liesch, J.M., Goetz, M.A., Jenkins, R.G., Nallin-Omstead M., Silverman, K.C., Bills, G.F., Mosley, RT., Gibbs, J.B., Albers-Schonberg G., Lingham, R.B.(1993) Isolation and structure of chaetomellic acid A and B from Chaetomella acustiseta: famesyl pyrophosphate mimics inhibitors of Ras famesyl-protein transderase.Tetrahedron. 49: 5917-5926   DOI   ScienceOn
6 Qian, Y., Sebti, S. M. and Hamilton, A D. (1997) Famesyltransferase as a target for anticancer drug design. John Wiley & Sons, Inc. Biopoly. 43: 25-41   DOI   ScienceOn
7 Kwon, B. M., Cho, Y K, Lee, S. H., Nam, J. Y, Bok, S. H., Chun S. K, Kim, J. A and Lee, I. R (1996) 2-Hydroxycinnamaldehyde from stem bark of Cinnamomum cassia. Planta Med. 62: 183-184   DOI   PUBMED
8 Kohl, N. E., Wilson, F. R, Mosser, S. D., Giuliani, E. A., DeSolms, S. J., Conner, M. W., Anthony, N. J., Holtz, W. J., Gomez, R P.,Lee, T.J., Smith, R. L., Hartman, G. D., Gibbs, J. B. and Oliff, A. (1994) Protein Famesy1transferase Inhibitors Block the Growth of ras-Dependent Tumors in Nude Mice. Proc. Natl. Acad. Sci. U.S.A. 91: 9141-9145   DOI   ScienceOn
9 Kwon, B. M., Lee, S. H., Kim, K S., Lee, I. R, Hong, U. C. and Bok, S. H. (1997) Bioorganic & Med. Chem. Lett. 7: 971-974   DOI   ScienceOn
10 Jayasuriya, H., Silverman, K. C., Zink, D. L., Jenkins, R. G., Sanchez, M., Pelaez, F., Vilella, D., Lingham, R. B. and Singh, S. B. (1998) Clavaric acid: A triterpenoid inhibitor of famesyl protein transferase from Clavariadelphus truncates. J. Nat. Prod. 61: 1568-1570   DOI   ScienceOn
11 Reiss, Y., Goldstein, J. L., Seabra, M. C, Casey, P. J. and Brown, M. S. (1990) Inhibition of purified $p21^{ras}$ famesyl: protein transferase by Cys-AAX tetrapeptides. Cell. 62: 8188
12 Johnston, S., Ellis, P. Houston, S. et al.: (2000) A phase II study of the famesyltransferase inhibitor Rl15777 in patients with advanced breast cancer[abstract]. Proe. Am. Soc. Oncol.19: 83a
13 Tamanoi, F, Gau, C. L., Jiang, C, Edamatsu, H. and KatoStankiewicz, J. (2001) Protein famesylaion in mammalian cells: effects of famesyltransferase inhibitors on cancer cells. Cell. Mol. Life. Sci. 58: 1636-1649   DOI   ScienceOn