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Evidence-Based Complementary and Alternative Medicine
Volume 2011 (2011), Article ID 215035, 10 pages
Original Article

Ellagic Acid, the Active Compound of Phyllanthus urinaria, Exerts In Vivo Anti-Angiogenic Effect and Inhibits MMP-2 Activity

1Department of Chinese Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan
2Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA
3School of Pharmacy, College of Medicine, National Taiwan University, Taipei 106, Taiwan
4Chinese Herbal Pharmacy, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan
5Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan 333, Taiwan

Received 8 May 2009; Accepted 19 October 2009

Copyright © 2011 Sheng-Teng Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. State Administration of Traditional Chinese Medicine (People's Republic of China) Chinese Materia Medica, vol. 4, Shanghai Scientific and Technical Publishers, Shanghai, China, 1st edition, 1999.
  2. K. J. Jeena, K. L. Joy, and R. Kuttan, “Effect of Emblica officinalis, Phyllanthus amarus and Picrorrhiza kurroa on N-nitrosodiethylamine induced hepatocarcinogenesis,” Cancer Letters, vol. 136, no. 1, pp. 11–16, 1999. View at Publisher · View at Google Scholar
  3. S.-T. Huang, R.-C. Yang, M.-Y. Chen, and J.-H. S. Pang, “Phyllanthus urinaria induces the Fas receptor/ligand expression and ceramide-mediated apoptosis in HL-60 cells,” Life Sciences, vol. 75, no. 3, pp. 339–351, 2004. View at Publisher · View at Google Scholar · View at PubMed
  4. S.-T. Huang, R.-C. Yang, and J.-H. S. Pang, “Aqueous extract of Phyllanthus urinaria induces apoptosis in human cancer cells,” American Journal of Chinese Medicine, vol. 32, no. 2, pp. 175–183, 2004. View at Publisher · View at Google Scholar
  5. S.-T. Huang, R.-C. Yang, L.-J. Yang, P.-N. Lee, and J.-H. S. Pang, “Phyllanthus urinaria triggers the apoptosis and Bcl-2 down-regulation in Lewis lung carcinoma cells,” Life Sciences, vol. 72, no. 15, pp. 1705–1716, 2003. View at Publisher · View at Google Scholar
  6. S.-T. Huang, R.-C. Yang, P.-N. Lee et al., “Anti-tumor and anti-angiogenic effects of Phyllanthus urinaria in mice bearing Lewis lung carcinoma,” International Immunopharmacology, vol. 6, no. 6, pp. 870–879, 2006. View at Publisher · View at Google Scholar · View at PubMed
  7. M. Xu, Z.-J. Zha, X.-L. Qin, X.-L. Zhang, C.-R. Yang, and Y.-J. Zhang, “Phenolic antioxidants from the whole plant of Phyllanthus urinaria,” Chemistry and Biodiversity, vol. 4, no. 9, pp. 2246–2252, 2007. View at Publisher · View at Google Scholar · View at PubMed
  8. J.-S. Silvestre, Z. Mallat, R. Tamarat, M. Duriez, A. Tedgui, and B. I. Levy, “Regulation of matrix metalloproteinase activity in ischemic tissue by interleukin-10: role in ischemia-induced angiogenesis,” Circulation Research, vol. 89, no. 3, pp. 259–264, 2001. View at Google Scholar
  9. M. Björklund and E. Koivunen, “Gelatinase-mediated migration and invasion of cancer cells,” Biochimica et Biophysica Acta, vol. 1755, no. 1, pp. 37–69, 2005. View at Publisher · View at Google Scholar · View at PubMed
  10. H. L. Li, Flora of Taiwan (II). Editorial Committee of the Flora of Taiwan, Taiwan University, Taipei, Taiwan, 2nd edition, 1993.
  11. P. C. Brooks, R. A. F. Clark, and D. A. Cheresh, “Requirement of vascular integrin α(v)β3 for angiogenesis,” Science, vol. 264, no. 5158, pp. 569–571, 1994. View at Google Scholar
  12. C. Heusen and E. B. Dowdle, “Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates,” Analytical Biochemistry, vol. 102, pp. 196–202, 1980. View at Google Scholar
  13. P. Chomczynski and N. Sacchi, “Single-step method of RNA isolated by acid guanidium thiocyanate-phenol-chloroform extraction,” Analytical Biochemistry, vol. 162, pp. 156–159, 1987. View at Google Scholar
  14. H. Luo, L. Chen, Z. Li, Z. Ding, and X. Xu, “Frontal immunoaffinity chromatography with mass spectrometric detection: a method for finding active compounds from traditional Chinese herbs,” Analytical Chemistry, vol. 75, pp. 3994–3998, 2003. View at Google Scholar
  15. J. B. Calixto, A. R. S. Santos, V. Cechinel Filho, and R. A. Yunes, “A review of the plants of the Genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential,” Medicinal Research Reviews, vol. 18, no. 4, pp. 225–258, 1998. View at Publisher · View at Google Scholar
  16. L. Z. Zhang, Y. J. Guo, G. Z. Tu, F. Miao, and W. B. Guo, “Isolation and identification of a noval polyphenolic compound from Phyllanthus urinaria L,” China Journal of Chinese Materia Medica, vol. 25, no. 12, pp. 724–725, 2000. View at Google Scholar
  17. R. Isobe, T. Tanaka, G. I. Nonaka, and I. Nishioka, “A new method for structural study of hydrolyzable tannins by negative fast atom bombardment mass spectroscopy,” Chemical & Pharmaceutical Bulletin, vol. 37, pp. 1748–1750, 1989. View at Google Scholar
  18. T. Yoshida, H. Itoh, S. Matsunaga, R. Tanaka, and T. Okuda, “Tannins and related polyphenols of euphorbiaceous plants. IX. hydrolyzable tannins with 1C4 glucose core from Phyllanthus muel,” Chemical & Pharmaceutical Bulletin, vol. 40, pp. 53–60, 1992. View at Google Scholar
  19. Y.-J. Zhang, T. Nagao, T. Tanaka, C.-R. Yang, H. Okabe, and I. Kouno, “Antiproliferative activity of the main constituents from Phyllanthus emblica,” Biological and Pharmaceutical Bulletin, vol. 27, no. 2, pp. 251–255, 2004. View at Publisher · View at Google Scholar
  20. K. C. S. C. Liu, M.-T. Lin, S.-S. Lee, J.-F. Chiou, S. Ren, and E. J. Lien, “Antiviral tannins from two Phyllanthus species,” Planta Medica, vol. 65, no. 1, pp. 43–46, 1999. View at Google Scholar
  21. L. Zhang, Y. Guo, G. Tu, W. Guo, and F. Miao, “Studies on chemical constituents of Phyllanthus urinaria L,” China Journal of Chinese Materia Medica, vol. 25, pp. 615–617, 2000. View at Google Scholar
  22. L. Labrecque, S. Lamy, A. Chapus et al., “Combined inhibition of PDGF and VEGF receptors by ellagic acid, a dietary-derived phenolic compound,” Carcinogenesis, vol. 26, pp. 821–826, 2005. View at Google Scholar
  23. J. Forkman, “The role of angiogenesis in tumor growth,” Seminars in Cancer Biology, vol. 3, pp. 65–71, 1992. View at Google Scholar
  24. P. Carmeliet and R. K. Jain, “Angiogenesis in cancer and other diseases,” Nature, vol. 407, no. 6801, pp. 249–257, 2000. View at Publisher · View at Google Scholar · View at PubMed
  25. D. Hanahan and J. Folkman, “Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis,” Cell, vol. 86, no. 3, pp. 353–364, 1996. View at Publisher · View at Google Scholar
  26. D. E. Ingber, D. Prusty, J. V. Frangioni, E. J. Cragoe Jr., C. Lechene, and M. A. Schwartz, “Control of intracellular pH and growth by fibronectin in capillary endothelial cells,” Journal of Cell Biology, vol. 110, no. 5, pp. 1803–1811, 1990. View at Publisher · View at Google Scholar
  27. R. E. Seftor, E. A. Seftor, N. Koshikawa et al., “Cooperetive interactions of laminin 5 gamma 2 chain, matrix metaloproteinnase-2, and membrane type-1- matrix/meteloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma,” Cancer Research, vol. 61, pp. 6322–6327, 2001. View at Google Scholar
  28. T. Itoh, M. Tanioka, H. Yoshida, T. Yoshioka, H. Nishimoto, and S. Itohara, “Reduced angiogenesis and tumor progression in gelatinase A-deficient mice,” Cancer Research, vol. 58, no. 5, pp. 1048–1051, 1998. View at Google Scholar
  29. M. A. Lafleur, A. F Drew, E. L de Sousa et al., “Up regulation of matrix metalloproteinases (MMPs) in breast cancer xenografts: a major induction of stromal MMP-13,” International Journal of Cancer, vol. 114, pp. 544–554, 2005. View at Google Scholar
  30. F. Sabeh, I. Ota, K. Holmbeck et al., “Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP,” Journal of Cell Biology, vol. 167, no. 4, pp. 769–781, 2004. View at Publisher · View at Google Scholar · View at PubMed
  31. E. V. Yang, A. K. Sood, M. Chen et al., “Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells,” Cancer Research, vol. 66, no. 21, pp. 10357–10364, 2006. View at Publisher · View at Google Scholar · View at PubMed
  32. K. Kunimasa, M. R. Ahn, T. Kobayashi et al., “Brazilian propolis suppresses angiogenesis by inducing apoptosis in tube-forming endothelial cells through inactivation of survival signal ERK1/2,” Evidence-Based Complementary and Alternative Medicine. In press.
  33. N. Matsunaga, Y. Chikaraishi, M. Shimazawa, S. Yokota, and H. Hara, “Vaccinium myrtillus (bilberry) extracts reduce angiogenesis in vitro and in vivo,” Evidence-Based Complementary and Alternative Medicine, vol. 7, no. 1, pp. 47–56, 2007. View at Google Scholar
  34. E. M. Daniel, A. S. Kropnick, Y. H. Heur, J. A. Blinzler, R. W. Nims, and G. D. Stoner, “Extraction, stability, and quantitation of ellagic acid in various fruit and nuts,” Journal of Food Composition and Analysis, vol. 2, pp. 338–349, 1990. View at Google Scholar
  35. D. H. Han, M. J. Lee, and J. H. Kim, “Antioxidant and apoptosis-inducing activities of ellagic acid,” Anticancer Research, vol. 26, no. 5 A, pp. 3601–3606, 2006. View at Google Scholar
  36. J. N. Losso, R. R. Bansode, A. Trappey II, H. A. Bawadi, and R. Truax, “In vitro anti-proliferative activities of ellagic acid,” Journal of Nutritional Biochemistry, vol. 15, no. 11, pp. 672–678, 2004. View at Publisher · View at Google Scholar · View at PubMed
  37. S. U. Mertens-Talcott, S. T. Talcott, and S. S. Percival, “Low concentrations of quercetin and ellagic acid synergistically influence proliferation, cytotoxicity and apoptosis in MOLT-4 human leukemia cells,” Journal of Nutrition, vol. 133, no. 8, pp. 2669–2674, 2003. View at Google Scholar
  38. N. P. Seeram, W. J. Aronson, Y. Zhang et al., “Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland,” Journal of Agricultural and Food Chemistry, vol. 55, no. 19, pp. 7732–7737, 2007. View at Publisher · View at Google Scholar · View at PubMed
  39. W. Hornebeck, H. Emonard, J.-C. Monboisse, and G. Bellon, “Matrix-directed regulation of pericellular proteolysis and tumor progression,” Seminars in Cancer Biology, vol. 12, no. 3, pp. 231–241, 2002. View at Publisher · View at Google Scholar
  40. D. A. Mayes, Y. Hu, Y. Teng et al., “PAX6 suppresses the invasiveness of glioblastoma cells and the expression of the matrix metalloproteinase-2 gene,” Cancer Research, vol. 66, no. 20, pp. 9809–9817, 2006. View at Publisher · View at Google Scholar · View at PubMed
  41. Y. Jo, J. Yeon, H.-J. Kim, and S.-T. Lee, “Analysis of tissue inhibitor of metalloproteinases-2 effect on pro-matrix metalloproteinase-2 activation by membrane-type 1 matrix metalloproteinase using baculovirus/insect-cell expression system,” Biochemical Journal, vol. 345, no. 3, pp. 511–519, 2000. View at Publisher · View at Google Scholar
  42. M. M. Bernardo and R. Fridman, “TIMP-2 (tissue inhibitor of metalloproteinase-2) regulates MMP-2 (matrix metalloproteinase-2) activity in the extracellular environment after pro-MMP-2 activation by MT1 (membrane type 1)-MMP,” Biochemical Journal, vol. 374, pp. 739–745, 2003. View at Google Scholar
  43. S. Richardson, G. Neama, T. Phillips et al., “Molecular characterization and partial cDNA cloning of facilitative glucose transporters expressed in human articular chondrocytes; stimulation of 2-deoxyglucose uptake by IGF-I and elevated MMP-2 secretion by glucose deprivation,” Osteoarthritis and Cartilage, vol. 11, pp. 92–101, 2003. View at Google Scholar