Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
권호 표지

Farnesyl Protein Transferase Inhibitory Components of Lithospermum erythrorhizon

  • Kim, Seong-Jin (College of Pharmacy, Woosuk University) ;
  • Kwon, Byoung-Mog (Korea Research Institute of Bioscience and Biotechnology, KIST) ;
  • Kim, Sung-Hoon (Lab. of Angiogenesis and Chemoprevention, Department of Oriental Pathology, College of Oriental Medicine, Kyunghee University) ;
  • Baek, Nam-In (Graduate School of Biotechnology & Plant Metabolism Research Center, KyungHee University) ;
  • Yang, Jae-Heon (College of Pharmacy, Woosuk University) ;
  • Lee, Jeong-Joo (College of Pharmacy, Woosuk University) ;
  • Lee, Sa-Im (College of Pharmacy, Woosuk University) ;
  • Kwon, Young-Ee (College of Pharmacy, Woosuk University) ;
  • Park, Hee-Wook (College of Pharmacy, Woosuk University) ;
  • Lee, Jae-Hyeok (Depart. of Oriental Pharmaceutical Development, Nambu University) ;
  • Park, Jeong-Suk (Depart. of Oriental Alternative Medicine, Nambu University) ;
  • Kim, Dae-Keun (College of Pharmacy, Woosuk University)
  • Published : 2007.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

The methanolic extract of the roots of Lithospermum erythrorhizon (Boraginaceae) was found to show inhibitory activity towards farnesyl protein transferase (FPTase). Bioassay-guided fractionation of the methanolic extract resulted in the isolation of three naphthoquinone compounds, as inhibitors of FPTase. These compounds inhibited the FPTase activity in a dose-dependent manner.

Keywords

References

  1. Cho, M.-H., Paik, Y.-S., and Hahn, T.-R., Propionylshikonin rom the roots of Lithospermum erythrorhizon. Arch. Pharm. Res., 22, 414-416 (1999) https://doi.org/10.1007/BF02979068
  2. Chung, M.-S. and Lee, M.-S., Stability and sensory evaluation of naphtoquinone pigments from the roots of Lithospermum erythrorhizon. Korean J. Food Sci. Technol., 26, 152-156 (1994)
  3. Doll, R.J., Kirschmeier, P., and Bishop, W.R., Farnesyltransferase inhibitors as anticancer agents: Critical crossroads. Curr. Opin. Drug Discov. Devel. 7, 478-486 (2004)
  4. Gibbs, J.B., Anticancer drug targets: growth factors and growth factor signaling. J. Clin. Invest. 105, 9-13 (2000) https://doi.org/10.1172/JCI9084
  5. Gibbs, J.B., Oliff, A., and Kohl, N.E., Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic. Cell 77, 175-178 (1994) https://doi.org/10.1016/0092-8674(94)90308-5
  6. Gibbs, J.B., Pompliano, D.L., Mosser, S.D., Rands, E., Lingham, R.B., Singh, S.B., Scolnick, E.M., Kohl, N.E., and Oliff, A., Selective inhibition of farnesyl-protein transferase blocks ras processing in vivo. J. Biol. Chem. 268, 7617-7620 (1993)
  7. Hwang, S.Y., Hwang, B.Y., Kang, S.S., Kim, C.M., Park, J.H., Bae K.H., Son, K.H., Lee, S.H., and Chang, S.Y., Isolation and quantitative analysis of acetylshikonin from Lithospermi Radix. Kor. J. Pharmacogn. 31, 295-299 (2000)
  8. Inoue, K., Akaji, M., and Inouye, H., Quinones and related compounds in higher plants. XXI. New findings on the proton and carbon-13 nuclear magnetic resonance spectra of shikonin. Chem. Pharm. Bull. 33, 3993- 3997 (1985) https://doi.org/10.1248/cpb.33.3993
  9. Kim, H. and Ahn, B.-Z., Antitumor effects of acetylshikonin and some synthesized naphtharazin on L1210 and S-180 system. Yakhak Hoeji 34, 262-266 (1990)
  10. Kimura, T., But, P.P.H., Guo, J.-X., and Sung, C.K., International collation of traditional an folk medicine. Part I, World Scientific, Singapore, p. 137-138 (1996)
  11. Kohl, N.E., Wilson, F.R., Mosser, S.D., Giulani, E.A., De Solms, 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., Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice. Proc. Natl. Acad. Sci. USA. 91, 9141-9145 (1994)
  12. Kundakovic, T., Fokialakis, N., Dobric, S., Pratsinis, H., Kletsas, D., Kovacevic, N., and Chinou, I., Evaluation of the anti-inflammatory and cytotoxic activities of naphthazarine derivatives from Onosma leptantha. Phytomed. 13, 290-294 (2006) https://doi.org/10.1016/j.phymed.2004.10.009
  13. Lee, J.-H. And Ahn, B.-Z., Antineoplastic natural products and the analogues (Xi); Cytotoxsic activity against L1210 cells of some raw drugs from the Oriental medicine and folklore. Kor. J. Pharmacogn. 17, 286-291 (1986)
  14. Lee, S.H., Kim, H.K, Kang, H.M., Seo, J.M., Son, K.H., Lee, H.S., and Kwon, B.M., Arteminolides B, C and D, new inhibitors of farnesyl protein transferase from Artemisia argyi. J. Org. Chem. 67, 7670-7675 (2002) https://doi.org/10.1021/jo020299z
  15. Lowy, D.R. and Willumsen, B.M., Function and regulation of Ras. Annu. Rev. Biochem. 62, 851-891 (1993) https://doi.org/10.1146/annurev.bi.62.070193.004223
  16. Morimoto, I. and Hirat, Y., New naphthoquinone derivatives from Lithospermum erythrorhizon. Tetrahedron Lett. 3677-3680 (1966)
  17. Morimoto, I., Kishi, T., Ikegami, S., and Hirata, Y., Naphtohquinone derivatives from Lithospermum erythrorhizon Siebold et Zuccarint. Tetrahedron Lett. 4737-4739 (1965)
  18. Oliff. A., Farnesyltransferase inhibitors: targeting the molecular basis of cancer. Biochim. Biophys. Acat 1423, C19-C30 (1999)
  19. Oh, H.-M., Choi, S.-K., Lee, J. M., Lee, S.-K., Kim, H.-Y., Han, D.C., Kim, H.-M., Son, K.-H., and Kwon, B.-M., Cyclopentenediones, inhibitors of farnesyl protein transferase and anti-tumor compounds, isolated from the fruit of Lindera erythrocarpa Makino. Bioorg. Med. Chem. 13, 6182-6187 (2005) https://doi.org/10.1016/j.bmc.2005.06.029
  20. Oh, H.M., Kwon, B.M., Baek, N.I., Kim, S.H., Chung, I.S., Park, M.H., Park, H.W., Lee, J.H., Park, H.W., Kim, E.J., and Kim, D.K., Inhibitory activity of isorhamnetin from Persicaria thunbergii on farnesyl protein transferase. Arch. Pharm. Res. 28, 169-171 (2005) https://doi.org/10.1007/BF02977709
  21. Omer, C.A., Chen, Z., Diehl, R.E., Conner, M.W., Chen, H.Y., Trumbauer, M.E., Gopal-Truter, S., Seeburger, G., Bhimnathwala, H., Abrams, M.T., Davide, J.P., Ellis, M.S., Gibbs, J.B., Greenberg, I., Koblan, K.S., Kral, A.M., Liu, D., Lobell, R.B., Miller, P.J., Mosser, S.D., O'Neill, T.J., Rands, E., Schaber, M.D., Senderak, E.T., Oliff, A., and Kohl, N.E., Mouse mammary tumor virus-Ki-rasB transgenic mice develop mammary carcinomas that can be growth-inhibited by a farnesyl:protein transferase inhibitor. Cancer Res. 60, 2680-2688 (2000)
  22. Reiss, Y., Goldstein, J.L., Seabra, M.C., Casey, P.J., and Brown, M.S., Inhibition of purified p21 Ras farnesyl protein transferase by Cys- AAX tetrapeptides. Cell 62, 81-88 (1990) https://doi.org/10.1016/0092-8674(90)90242-7
  23. Sepp-Lorenzino, L., Tjaden, G., Moasser, M.M., Timaul, N., Ma, Z., Kohl, N.E., Gibbs, J.B., Oliff, A., Rosen, N., and Scher, H.I., Farnesyl : protein transferase inhibitors as potential agents for the management of human prostate cancer. Prostate Cancer Prostatic Dis. 4, 33-43 (2001) https://doi.org/10.1038/sj.pcan.4500491
  24. Suzanne, C. M., S. Jane deSolms, Anthony, W.S., Marc, T.A., Terrence, M.C., Joseph, P.D., Kelly, A.H., John, H.H., Kenneth, S.K., Nancy, E.K., Robert, B.L., Ronald, G.R., and Samuel, L.G., Diaryl ether inhibitors of farnesyl-protein transferase. Bioorg. Med. Chem. Lett. 11, 1257-1260 (2001) https://doi.org/10.1016/S0960-894X(01)00162-7
  25. Tanaka, S., Tajima, M., Tsukada, M., and Tabata, M., A comparative study on anti-inflammatory activities of the enantiomers, shikonin and alkannin. J. Nat. Prod. 49, 466-469 (1986) https://doi.org/10.1021/np50045a014