Inhibitory Effects of Paeonia suffruticosa Andrews Extracts on VEGF Binding to VEGF Receptor

  • Lee, Hak-Kyo (Gyonggi Regional Research Center, Hankyong National University) ;
  • Lee, Sung-Jin (Gyonggi Regional Research Center, Hankyong National University)
  • 발행 : 2007.06.30

초록

Tumor angiogenesis is a critical step f3r the growth and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) is the most important angiogenic molecule associated with tumor-induced neovascularization. VEGF exerts its activity through binding to its receptor tyrosine kinase, KDR/Flk-1, expressed on the surface of endothelial cells. This study was carried out to investigate inhibitory effect of extracts from root cortex of Paeonia suffruticosa Andrews on VEGF binding to VEGF receptor. The MeOH extract from P. suffrutiocosa Andr. inhibited the binding of KDR/Flk-1-Fc to immobilized VEGF$_{165}$ more than 45% at the concentration of 100 ${\mu}$g/mL. The MeOH extract was further fractionated into n-hexane, ethyl acetate, n-BuOH, and aqueous fractions. Among the four fractions, the ethyl acetate fraction from the root cortex of P. suffruticosa Andr. exhibited highly effective inhibition (${\approx}$ 79% inhibition) and then n-BuOH fraction (${\approx}$ 45% inhibition) on the binding of KDR/Flk-1-Fc to immobilized VEGF$_{165}$ at the concentration of 100 ${\mu}$g/mL. The ethyl acetate fraction from the root cortex of P. suffruticosa Andr. more efficiently blocked VEGF-induced human umbilical vein endothelial cell proliferation, than the growth of HT1080 human fibrosarcoma. Our results suggest that P. suffruticosa Andr. may be used as a candidate fur developing anti-angiogenic agent.

키워드

참고문헌

  1. Atsumi, S., Nosaka, C., Ochi, Y., Iinuma, H., and Umezawa, K., Inhibition of experimental metastasis by an $\alpha$-glucosidase inhibitor, 1,6-epi-cyclophellitol. Cancer Res. 53, 4896-4899 (1993)
  2. Au, T.K., Lam, T.L., Ng, T.B., Fong, W.P., and Wan, D.C., A Comparison of HIV-1 integrase inhibition by aqueous and methanol extracts of Chinese medicinal herbs. Life Science 68, 1687-1694 (2001) https://doi.org/10.1016/S0024-3205(01)00945-6
  3. Bae, D.G., Gho, Y.S., Yoon, W.H., and Chae, C.B., Arginine-rich anti-vascular endothelial growth factor peptides inhibit tumor growth and metastasis by blocking angiogenesis, J. Biol. Chem. 275, 13588-13596 (2000) https://doi.org/10.1074/jbc.275.18.13588
  4. Boehm-Viswanathan, T., Is angiogenesis inhibition the Holy Grail of cancer therapy? Curr. Opin. Oncol. 12, 89-94 (2000) https://doi.org/10.1097/00001622-200001000-00015
  5. Carmeliet, P., Ferreira, V., Breier, G., Pollefeyt, S., Kieckens, L., Gertsenstein, M., Fahrig, M., Vandenhoeck, A., Harpal, K., Eberhardt, C., Declercq, C., Pawling, J., Moons, L., Collen, D., Risau, W., and Nagy, A., Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele, Nature 380, 435-439 (1996) https://doi.org/10.1038/380435a0
  6. De Vries, C.J., Escobedo, A., Ueno, H., Houck, K., Ferrara, N., and Williams, L.T., The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor, Science 255, 989-991 (1992) https://doi.org/10.1126/science.1312256
  7. Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O'Shea, K. S., Powell-Braxton, L., Hillan, K.J., and Moore, M.W., Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene, Nature 380, 439-442 (1996) https://doi.org/10.1038/380439a0
  8. Folkman, J., What is the evidence that tumors are angiogenesisdependent? J. Natl. Cancer Inst. 82, 4-6 (1991)
  9. Goldman, C.K., Kendall, R.I., Cabrera, G., Soroceanu, L., Heike, Y., Gillespie, G.Y., Siegel, G.P., Mao, X., Bett, A.J., Huckle, W.R., Thomas, K.A., and Curiel, D.T., Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate, Proc. Natl. Acad. Sci. USA 95, 8795-8800 (1998)
  10. Hsiang, C.Y., Hsieh, C.L., Wu, S.L., Lai, I.L., and Ho, T.Y., Inhibitory effect of anti-pyretic and anti-inflammatory herbs on herpes simplex virus replication. Am. J. Chin. Med. 29, 459-467 (2001) https://doi.org/10.1142/S0192415X01000472
  11. Khatri, J.J., Johnson, C., Magid, R., Lessner, S.M., Laude, K.M., Dikalov, S.I., Harrison D.G., Sung H.J., Rong, Y., and Galis Z.S., Vascular oxidant stress enhances progression and angiogenesis of experimental atheroma. Circulation 109, 520-525 (2004) https://doi.org/10.1161/01.CIR.0000109698.70638.2B
  12. Kim, C.W., Lee, H.M., Lee, T.H., Kang, C., Kleinman, H.K., and Gho, Y.S., Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin, Cancer Res. 62, 6312-6317 (2002a)
  13. Kim, K.J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H.S., and Ferrara, N., Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo, Nature 362, 841-844 (1993) https://doi.org/10.1038/362841a0
  14. Kim, Y.M., Hwang, S., Kim, Y.M., Pyun, B.J., Kim, T.Y., Lee, S.T., Gho, Y.S., and Kwon, Y.G., Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1, J. Biol. Chem. 277, 27872-27879 (2002b) https://doi.org/10.1074/jbc.M202771200
  15. Kondo, T., Ohta, T., Igura, K., Hara, Y., and Kaji, K., Tea catechins inhibit angiogenesis in vitro, measured by human endothelial cell growth, migration and tube formation, through inhibition of VEGF receptor binding, Cancer Lett. 180, 139-144 (2002) https://doi.org/10.1016/S0304-3835(02)00007-1
  16. Lamy, S., Gingras, D., and Beliveau, R., Green tea catechins inhibit vascular endothelial growth factor receptor phosphorylation, Cancer Res. 62, 381-385 (2002)
  17. Lee, S.E., Hwang, H.J., Ha, J.S., Jeong, H.S., and Kim, J.H., Screening of medicinal plant extracts for antioxidant activity. Life Sci. 73, 167-79 (2003) https://doi.org/10.1016/S0024-3205(03)00259-5
  18. Lee, S.J. and Ji, S.T., Inhibitory Effects of Paeonia suffruticosa extracts on maltase and Sucrase. Nat. Prod. Sci. 11, 127-130 (2005)
  19. Leibovich, S.J., Polverini, P.J., Fong, T.W., Harlow, L.A., and Koch, A.E., Production of angiogenic activity by human monocytes requires an Larginine/ nitric oxide-synthase-dependent effector mechanism. Proc. Natl. Acad. Sci. USA 91, 4190-4194 (1994)
  20. Leung, D.W., Cachianes, G., Kuang, W.J., Goeddel, D.V., and Frrarara, N., Vascular endothelial growth factor is a secreted angiogenic mitogen, Science 246, 1306-1309 (1989) https://doi.org/10.1126/science.2479986
  21. Lin, H.C., Ding, H.Y., and Wu, Y.C., Two novel compounds from Paeonia suffructicosa. J. of Nat. Prod. 61, 343-346 (1998) https://doi.org/10.1021/np9704258
  22. Millauer, B., Shawver, L.K., Plate, K.H., Risau, W., and Ullrich, A., Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant, Nature 367, 576-579 (1994) https://doi.org/10.1038/367576a0
  23. Millauer, B., Wizigmann-Voos, S., Schnurch, H., Martinez, R., Moller, N. P., Risau, W., and Ullrich, A., High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72, 835-846 (1993) https://doi.org/10.1016/0092-8674(93)90573-9
  24. Ncosia, R.F., Tchao, R., and Leighton, J., Angiogenesis-dependent tumor spread in reinforced fibrin clot culture. Cancer Res. 43, 2159-2166 (1983)
  25. Park, H.J. and Choi, M.Y., In vitro antiinflamatory activity of paeonol from the essential oil and its derivative methylpaeonol. Kor. J. Pharmacogn. 26, 116-120 (2005)
  26. Pili, R., Cang, J., Partis, R.A., Mueller, R.A., Chrest, F.J., and Passaniti, A. The $\alpha$-glucosidase inhibitor castanospermine alters endothelial cell glycosylation, prevents angiogenesis, and inhibits tumor growth. Cancer Res. 55, 2920-2926 (1995)
  27. Risau, W., Angiogenic growth factors. Prog. Growth Factor Res. 2, 71-79 (1990) https://doi.org/10.1016/0955-2235(90)90010-H
  28. Shalaby, F., Rossant, J., Yamaguch, T.P., Gertsenstein, M., Wu, X.F., Breitman, M.L., and Schuh, S.C., Failure of blood-island formation vasculogenesis in Flk-1-deficient mice, Nature 376, 62-66 (1995) https://doi.org/10.1038/376062a0
  29. Ziche, M., Morbidelli, L., Masini, E., Amerini, S., Granger, H.J., Maggi, C.A., Geppetti, P., and Ledda, F., Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J. Clin. Invest. 94, 2036-2044 (1994) https://doi.org/10.1172/JCI117557