Korean Journal of Pharmacognosy (생약학회지)

The Korean Society of Pharmacognosy (한국생약학회)
권호 표지

Screening of Inhibitory Activity of Plant Extracts against Farnesyl Protein Transferase

식물추출물의 파네실 전달효소 저해활성 검색

  • 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)
  • 강현미 (한국생명공학연구원 항생물질연구실) ;
  • 이승호 (한국생명공학연구원 항생물질연구실) ;
  • 유시용 (한국화학연구원) ;
  • 손광희 (한국생명공학연구원 항생물질연구실) ;
  • 양덕조 (충북대학교 자연과학대학 생명과학부) ;
  • 권병목 (한국생명공학연구원 항생물질연구실)
  • Published : 2003.03.30
Download PDF
⟨ Previous Next ⟩

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

References

  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 https://doi.org/10.1016/S1040-8428(99)00053-0
  2. 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 https://doi.org/10.1002/(SICI)1097-0282(1997)43:1<25::AID-BIP4>3.0.CO;2-2
  3. 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 https://doi.org/10.1073/pnas.91.19.9141
  4. 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
  5. 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 https://doi.org/10.1126/science.8316833
  6. 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 https://doi.org/10.1021/np980200c
  7. 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 https://doi.org/10.1016/S0040-4020(01)87178-7
  8. 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 https://doi.org/10.1021/jo980919p
  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 https://doi.org/10.1016/S0960-894X(97)00139-X
  10. 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 https://doi.org/10.1055/s-2006-957851
  11. 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 https://doi.org/10.1007/PL00000802
  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. 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