Cancer and Metastasis Reviews

, Volume 31, Issue 1–2, pp 323–351 | Cite as

Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities



Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate, and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin, apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin, daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell–cell attachment, tissue-barrier degradation, migration, invasion, cell–matrix adhesion, and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on anti-angiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.


Angiogenesis Chemoprevention Flavonoid Invasion Metastasis 







CXC chemokine receptor 4




Extracellular matrix




Epidermal growth factor receptor


Extracellular matrix metalloproteinase inducer


Epithelial–mesenchymal transition


Estrogen receptor


Epidermal growth factor receptor-related protein B2


Focal adhesion kinase


Forkhead box O3


Hepatocyte growth factor


Hypoxia-inducible factor




Heat shock protein


Human umbilical vein endothelial cells


Inducible nitric oxide synthase




Lewis lung carcinoma


MAP kinase-activated protein kinase 2


Murine double minute 2


Mesenchymal–epithelial transition


Matrix metalloproteinases


Membrane type-1 MMP


Metastasis-associated protein 3


Mucin 1, cell surface-associated






Plasminogen activator inhibitor


Platelet endothelial cell adhesion molecule


Phorbol 12-myristate 13-acetate


Protein kinase C


Prostaglandin E2


Polymorphonuclear phagocytes


Protease nexin-II


Prostate-specific antigen


Receptor activator of nuclear factor-kB ligand


Reversion-inducing cysteine-rich protein with kazal motifs


Zinc finger protein SNAI2


Tissue inhibitor metalloproteinase protein


Transgenic adenocarcinoma of mouse prostate


Urokinase plasminogen activator


Urokinase plasminogen activator receptor


Vasodilator-stimulated phosphoprotein


Vascular endothelial growth factor


Zinc finger E-box-binding homeobox 1


  1. 1.
    Weiss, L. (1990). Metastatic inefficiency. Advances in Cancer Research, 54, 159–211.PubMedGoogle Scholar
  2. 2.
    Liotta, L. A., Steeg, P. S., & Stetter-Stevenson, W. G. (1991). Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell, 64, 327–336.PubMedGoogle Scholar
  3. 3.
    Condeelis, J., & Segall, J. E. (2003). Intravital imaging of cell movement in tumours. Nature Reviews. Cancer, 3, 921–930.PubMedGoogle Scholar
  4. 4.
    Van Sumere, C. F. (1989). Phenols and phenolic acids. In J. B. Harborne (Ed.), Methods in plant biochemistry, volume 1 (Plant phenolics, pp. 29–74). London: Academic.Google Scholar
  5. 5.
    Shahidi, F. (2000). Antioxidants in food and food antioxidants. Die Nahrung, 44, 158–163.PubMedGoogle Scholar
  6. 6.
    Shahidi, F. (2002). Antioxidants in plants and oleaginous seeds. In M. J. Morello, F. Shahidi, & C. T. Ho (Eds.), Free radicals in food: Chemistry, nutrition, and health effects, ACS symposium series 807 (pp. 162–175). Washington, DC: American Chemical Society.Google Scholar
  7. 7.
    Cook, N. C., & Samman, S. (1996). Flavonoids—chemistry, metabolism, cardioprotective effects, and dietary sources. The Journal of Nutritional Biochemistry, 7, 66–76.Google Scholar
  8. 8.
    Ververidis, F., Trantas, E., Douglas, C., Vollmer, G., Kretzschmar, G., & Panopoulos, N. (2007). Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health. Biotechnology Journal, 2, 1214–1234.PubMedGoogle Scholar
  9. 9.
    Sliva, D. (2008). Suppression of cancer invasiveness by dietary compounds. Mini Reviews in Medicinal Chemistry, 8, 677–688.PubMedGoogle Scholar
  10. 10.
    Weng, C. J., & Yen, G. C. (2012). Chemopreventive effects of dietary phytochemicals against cancer invasion and metastasis: Phenolic acids, monophenol, polyphenol, and their derivatives. Cancer Treatment Reviews, 38, 76–87.PubMedGoogle Scholar
  11. 11.
    Christofori, G. (2006). New signals from the invasive front. Nature, 441, 444–450.PubMedGoogle Scholar
  12. 12.
    Thiery, J. P. (2002). Epithelial–mesenchymal transitions in tumour progression. Nature Reviews. Cancer, 2, 442–454.PubMedGoogle Scholar
  13. 13.
    Yang, J., & Weinberg, R. A. (2008). Epithelial–mesenchymal transition: At the crossroads of development and tumor metastasis. Developmental Cell, 14, 818–829.PubMedGoogle Scholar
  14. 14.
    Joo, Y., Rew, J., Park, C., & Kim, S. (2002). Expression of E-cadherin, alpha- and beta-catenins in patients with pancreatic adenocarcinoma. Pancreatology, 2, 129–137.PubMedGoogle Scholar
  15. 15.
    Nakajima, S., Doi, R., Toyoda, E., Tsuji, S., Wada, M., Koizumi, M., Tulachan, S. S., Ito, D., Kami, K., Mori, T., Kawaguchi, Y., Fujimoto, K., Hosotani, R., & Imamura, M. (2004). N-cadherin expression and epithelial–mesenchymal transition in pancreatic carcinoma. Clinical Cancer Research, 10, 4125–4133.PubMedGoogle Scholar
  16. 16.
    Sanders, D. S., Bruton, R., Darnton, S. J., Casson, A. G., Hanson, I., Williams, H. K., & Jankowski, J. (1998). Sequential changes in cadherin–catenin expression associated with the progression and heterogeneity of primary oesophageal squamous carcinoma. International Journal of Cancer, 79, 573–579.Google Scholar
  17. 17.
    Muzio, L. Lo, Pannone, G., Mignogna, M. D., Staibano, S., Mariggio, M. A., Rubini, C., Procaccini, M., Dolci, M., Bufo, P., Rosa, G. De, & Piattelli, A. (2004). P-cadherin expression predicts clinical outcome in oral squamous cell carcinomas. Histology and Histopathology, 19, 1089–1099.PubMedGoogle Scholar
  18. 18.
    Bachmann, I. M., Straume, O., Puntervoll, H. E., Kalvenes, M. B., & Akslen, L. A. (2005). Importance of P-cadherin, beta-catenin, and Wnt5a/frizzled for progression of melanocytic tumors and prognosis in cutaneous melanoma. Clinical Cancer Research, 11, 8606–8614.PubMedGoogle Scholar
  19. 19.
    Van Marck, V., Stove, C., Jacobs, K., Van den Eynden, G., & Bracke, M. (2011). P-cadherin in adhesion and invasion: Opposite roles in colon and bladder carcinoma. International Journal of Cancer, 128, 1031–1044.Google Scholar
  20. 20.
    Gamallo, C., Moreno-Bueno, G., Sarrio, D., Calero, F., Hardisson, D., & Palacios, J. (2001). The prognostic significance of P-cadherin in infiltrating ductal breast carcinoma. Modern Pathology, 14, 650–654.PubMedGoogle Scholar
  21. 21.
    Paredes, J., Stove, C., Stove, V., Milanezi, F., Van Marck, V., Derycke, L., Mareel, M., Bracke, M., & Schmitt, F. (2004). P-cadherin is upregulated by the antiestrogen ICI 182,780 and promotes invasion of human breast cancer cells. Cancer Research, 64, 8309–8317.PubMedGoogle Scholar
  22. 22.
    Stefansson, I. M., Salvesen, H. B., & Akslen, L. A. (2004). Prognostic impact of alterations in Pcadherin expression and related cell adhesion markers in endometrial cancer. Journal of Clinical Oncology, 22, 1242–1252.PubMedGoogle Scholar
  23. 23.
    Taniuchi, K., Nakagawa, H., Hosokawa, M., Nakamura, T., Eguchi, H., Ohigashi, H., Ishikawa, O., Katagiri, T., & Nakamura, Y. (2005). Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases. Cancer Research, 65, 3092–3099.PubMedGoogle Scholar
  24. 24.
    Gravdal, K., Halvorsen, O. J., Haukaas, S. A., & Akslen, L. A. (2007). A switch from E-cadherin to N-cadherin expression indicates epithelial to mesenchymal transition and is of strong and independent importance for the progress of prostate cancer. Clinical Cancer Research, 13, 7003–7011.PubMedGoogle Scholar
  25. 25.
    Tothill, R. W., Tinker, A. V., George, J., Brown, R., Fox, S. B., Lade, S., Johnson, D. S., Trivett, M. K., Etemadmoghadam, D., Locandro, B., Traficante, N., Fereday, S., Hung, J. A., Chiew, Y. E., Haviv, I., Australian Ovarian Cancer Study Group, Gertig, D., DeFazio, A., & Bowtell, D. D. (2008). Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clinical Cancer Research, 14, 5198–5208.PubMedGoogle Scholar
  26. 26.
    Imai, K., Hirata, S., Irie, A., Senju, S., Ikuta, Y., Yokomine, K., Harao, M., Inoue, M., Tsunoda, T., Nakatsuru, S., Nakagawa, H., Nakamura, Y., Baba, H., & Nishimura, Y. (2008). Identification of a novel tumor-associated antigen, cadherin 3/P-cadherin, as a possible target for immunotherapy of pancreatic, gastric, and colorectal cancers. Clinical Cancer Research, 14, 6487–6495.PubMedGoogle Scholar
  27. 27.
    Francí, C., Takkunen, M., Dave, N., Alameda, F., Gómez, S., Rodríguez, R., Escrivà, M., Montserrat-Sentís, B., Baró, T., Garrido, M., Bonilla, F., Virtanen, I., & García de Herreros, A. (2006). Expression of Snail protein in tumor-stroma interface. Oncogene, 25, 5134–5144.PubMedGoogle Scholar
  28. 28.
    Hipp, S., Walch, A., Schuster, T., Höfler, H., & Becker, K. F. (2008). Precise measurement of the E-cadherin repressor Snail in formalin-fixed endometrial carcinoma using protein lysate microarrays. Clinical & Experimental Metastasis, 25, 679–683.Google Scholar
  29. 29.
    Burk, U., Schubert, J., Wellner, U., Schmalhofer, O., Vincan, E., Spaderna, S., & Brabletz, T. (2008). A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Reports, 9, 582–589.PubMedGoogle Scholar
  30. 30.
    Chang, T. H., Tsai, M. F., Su, K. Y., Wu, S. G., Huang, C. P., Yu, S. L., Yu, Y. L., Lan, C. C., Yang, C. H., Lin, S. B., Wu, C. P., Shih, J. Y., & Yang, P. C. (2011). Slug confers resistance to the epidermal growth factor receptor tyrosine kinase inhibitor. American Journal of Respiratory and Critical Care Medicine, 183, 1071–1079.PubMedGoogle Scholar
  31. 31.
    Myatt, S. S., & Lam, E. W. (2007). The emerging roles of forkhead box (Fox) proteins in cancer. Nature Reviews. Cancer, 7, 847–859.PubMedGoogle Scholar
  32. 32.
    Humphries, M. J. (2000). Integrin structure. Biochemical Society Transactions, 28, 311–339.PubMedGoogle Scholar
  33. 33.
    Yamamoto, M., Bharti, A., Li, Y., & Kufe, D. (1997). Interaction of the DF3/MUC1 breast carcinoma-associated antigen and beta-catenin in cell adhesion. Journal of Biological Chemistry, 272, 12492–12494.PubMedGoogle Scholar
  34. 34.
    Huang, L., Chen, D., Liu, D., Yin, L., Kharbanda, S., & Kufe, D. (2005). MUC1 oncoprotein blocks glycogen synthase kinase 3beta-mediated phosphorylation and degradation of beta-catenin. Cancer Research, 65, 10413–10422.PubMedGoogle Scholar
  35. 35.
    Roy, L. D., Sahraei, M., Subramani, D. B., Besmer, D., Nath, S., Tinder, T. L., Bajaj, E., Shanmugam, K., Lee, Y. Y., Hwang, S. I. L., Gendler, S. J., & Mukherjee, P. (2011). MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition. Oncogene, 30, 1449–1459.PubMedGoogle Scholar
  36. 36.
    Sahai, E. (2007). Illuminating the metastatic process. Nature Reviews. Cancer, 7, 737–749.PubMedGoogle Scholar
  37. 37.
    Wyckoff, J. B., Jones, J. G., Condeelis, J. S., & Segall, J. E. (2000). A critical step in metastasis: In vivo analysis of intravasation at the primary tumor. Cancer Research, 60, 2504–2511.PubMedGoogle Scholar
  38. 38.
    Ghosh, M., Song, X., Mouneimne, G., Sidani, M., Lawrence, D. S., & Condeelis, J. S. (2004). Cofilin promotes actin polymerization and defines the direction of cell motility. Science, 304, 743–746.PubMedGoogle Scholar
  39. 39.
    Kleiner, D. E., & Stetler-Stevenson, W. G. (1999). Matrix metalloproteinases and metastasis. Cancer Chemotherapy and Pharmacology, 43, S41–S51.Google Scholar
  40. 40.
    Westermarck, J., & Kahari, V. M. (1999). Regulation of matrix metalloproteinase expression in tumor invasion. The FASEB Journal, 13, 781–792.Google Scholar
  41. 41.
    Friedl, P., & Wolf, K. (2003). Tumour-cell invasion and migration: Diversity and escape mechanisms. Nature Reviews. Cancer, 3, 362–374.PubMedGoogle Scholar
  42. 42.
    Rao, J. S. (2003). Molecular mechanisms of glioma invasiveness: The role of proteases. Nature Reviews. Cancer, 3, 489–501.PubMedGoogle Scholar
  43. 43.
    Yamamoto, H., Itoh, F., Iku, S., Adachi, Y., Fukushima, H., Sasaki, S., Mukaiya, M., Hirata, K., & Imai, K. (2001). Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: Clinicopathologic and prognostic significance of matrilysin expression. Journal of Clinical Oncology, 19, 1118–1127.PubMedGoogle Scholar
  44. 44.
    Chung, T. W., Moon, S. K., Lee, Y. C., Kim, J. G., Ko, J. H., & Kim, C. H. (2002). Enhanced expression of matrix metalloproteinase-9 by hepatitis B virus infection in liver cells. Archives of Biochemistry and Biophysics, 408, 147–154.PubMedGoogle Scholar
  45. 45.
    Muramatsu, T., & Miyauchi, T. (2004). Basigin (CD147): A multifunctional transmembrane protein involved in reproduction, neural function, inflammation and tumor invasion. Histology and Histopathology, 18, 981–987.Google Scholar
  46. 46.
    Jinga, D. C., Blidaru, A., Condrea, I., Ardeleanu, C., Dragomir, C., Szegli, G., Stefanescu, M., & Matache, C. (2006). MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer: Correlations with prognostic factors. Journal of Cellular and Molecular Medicine, 10, 499–510.PubMedGoogle Scholar
  47. 47.
    Tan, X., Egami, H., Nozawa, F., Abe, M., & Baba, H. (2006). Analysis of the invasion-metastasis mechanism in pancreatic cancer: Involvement of plasmin(ogen) cascade proteins in the invasion of pancreatic cancer cells. International Journal of Oncology, 28, 369–374.PubMedGoogle Scholar
  48. 48.
    Mazar, A. P. (2001). The urokinase plasminogen activator receptor (uPAR) as a target for the diagnosis and therapy of cancer. Anti-Cancer Drugs, 12, 387–400.PubMedGoogle Scholar
  49. 49.
    Sliva, D., Labarrere, C., Slivova, V., Sedlak, M., Lloyd, F. P., Jr., & Ho, N. W. (2002). Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells. Biochemical and Biophysical Research Communications, 298, 603–612.PubMedGoogle Scholar
  50. 50.
    Sidenius, N., & Blasi, F. (2003). The urokinase plasminogen activator system in cancer: Recent advances and implication for prognosis and therapy. Cancer and Metastasis Reviews, 22, 205–222.PubMedGoogle Scholar
  51. 51.
    Han, B., Nakamura, M., Mori, I., Nakamura, Y., & Kakudo, K. (2005). Urokinase-type plasminogen activator system and breast cancer (review). Oncology Reports, 14, 105–112.PubMedGoogle Scholar
  52. 52.
    Duggan, C., Kennedy, S., Kramer, M. D., Barnes, C., Elvin, P., McDermott, E., O’Higgins, N., & Duffy, M. J. (1997). Plasminogen activator inhibitor type 2 in breast cancer. British Journal of Cancer, 76, 622–627.PubMedGoogle Scholar
  53. 53.
    Sakakibara, T., Hibi, K., Koike, M., Fujiwara, M., Kodera, Y., Ito, K., & Nakao, A. (2005). Plasminogen activator inhibitor-1 as a potential marker for the malignancy of colorectal cancer. British Journal of Cancer, 93, 799–803.PubMedGoogle Scholar
  54. 54.
    Kang, H. G., Kim, H. S., Kim, K. J., Oh, J. H., Lee, M. R., Seol, S. M., & Han, I. (2007). RECK expression in osteosarcoma: Correlation with matrix metalloproteinases activation and tumor invasiveness. Journal of Orthopaedic Research, 25, 696–702.PubMedGoogle Scholar
  55. 55.
    Rao, A. R., Motiwala, H. G., & Karim, O. M. (2008). The discovery of prostate-specific antigen. BJU International, 101, 5–10.PubMedGoogle Scholar
  56. 56.
    Lilja, H. (2003). Biology of prostate-specific antigen. Urology, 62, 27–33.PubMedGoogle Scholar
  57. 57.
    Fuchs, E. (1882). Das Sarcom des Uvealtractus. In W. Braumueller (Ed.), Metastasenbildung (pp. 197–206). Vienna: Wilhelm Braumuller.Google Scholar
  58. 58.
    Paget, S. (1889). The distribution of secondary growths in cancer of the breast. Lancet, 1, 571–573.Google Scholar
  59. 59.
    Fidler, I. J. (2003). The pathogenesis of cancer metastasis: The ‘seed and soil’ hypothesis revisited. Nature Reviews. Cancer, 3, 453–458.PubMedGoogle Scholar
  60. 60.
    Ruoslahti, E., & Rajotte, D. (2000). An address system in the vasculature of normal tissues and tumors. Annual Review of Immunology, 18, 813–827.PubMedGoogle Scholar
  61. 61.
    Brown, D. M., & Metadherin, R. E. (2004). A cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell, 5, 365–374.PubMedGoogle Scholar
  62. 62.
    Muller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M. E., McClanahan, T., Murphy, E., Yuan, W., Wagner, S. N., Barrera, J. L., Mohar, A., Verástegui, E., & Zlotnik, A. (2001). Involvement of chemokine receptors in breast cancer metastasis. Nature, 410, 50–56.PubMedGoogle Scholar
  63. 63.
    Harbeck, B., Hüttelmaier, S., Schluter, K., Jockusch, B. M., & Illenberger, S. (2000). Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its interaction with actin. The Journal of Biological Chemistry, 275, 30817–30825.PubMedGoogle Scholar
  64. 64.
    McDougall, S. R., Anderson, A. R., & Chaplain, M. A. (2006). Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: Clinical implications and therapeutic targeting strategies. Journal of Theoretical Biology, 241, 564–589.PubMedGoogle Scholar
  65. 65.
    Bergers, G., & Benjamin, L. E. (2003). Tumorigenesis and the angiogenic switch. Nature Reviews. Cancer, 3, 401–410.PubMedGoogle Scholar
  66. 66.
    Kalluri, R. (2003). Basement membranes: Structure, assembly and role in tumour angiogenesis. Nature Reviews. Cancer, 3, 422–433.PubMedGoogle Scholar
  67. 67.
    Thurston, G. (2003). Role of Angiopoietins and Tie receptor tyrosine kinases in angiogenesis and lymphangiogenesis. Cell and Tissue Research, 314, 61–68.PubMedGoogle Scholar
  68. 68.
    Smith, T. G., Robbins, P. A., & Ratcliffe, P. J. (2008). The human side of hypoxia-inducible factor. British Journal of Haematology, 141, 325–334.PubMedGoogle Scholar
  69. 69.
    Harris, A. L. (2002). Hypoxia—a key regulatory factor in tumour growth. Nature Reviews. Cancer, 2, 38–47.PubMedGoogle Scholar
  70. 70.
    Sullivan, R., & Graham, C. H. (2007). Hypoxia-driven selection of the metastatic phenotype. Cancer and Metastasis Reviews, 26, 319–331.PubMedGoogle Scholar
  71. 71.
    Semenza, G. L. (2003). Targeting HIF-1 for cancer therapy. Nature Reviews. Cancer, 3, 721–732.PubMedGoogle Scholar
  72. 72.
    Semenza, G. L. (2007). Evaluation of HIF-1 inhibitors as anticancer agents. Drug Discovery Today, 12, 853–859.PubMedGoogle Scholar
  73. 73.
    Melillo, G. (2006). Inhibiting hypoxia-inducible factor 1 for cancer therapy. Molecular Cancer Research, 4, 601–605.PubMedGoogle Scholar
  74. 74.
    Steeg, P. S. (2006). Tumor metastasis: Mechanistic insights and clinical challenges. Nature Medicine, 12, 895–904.PubMedGoogle Scholar
  75. 75.
    Khan, N., & Mukhtar, H. (2007). Tea polyphenols for health promotion. Life Sciences, 81, 519–533.PubMedGoogle Scholar
  76. 76.
    Chacko, S. M., Thambi, P. T., Kuttan, R., & Nishigaki, I. (2010). Beneficial effects of green tea: A literature review. Chinese Medicine, 5, 13.PubMedGoogle Scholar
  77. 77.
    Cao, Y., Cao, R., & Brakenhielm, E. (2002). Antiangiogenic mechanisms of diet-derived polyphenols. The Journal of Nutritional Biochemistry, 13, 380–390.PubMedGoogle Scholar
  78. 78.
    Khan, N., Afaq, F., Saleem, M., Ahmad, N., & Mukhtar, H. (2006). Targeting multiple signaling pathways by green tea polyphenol (−)-epigallocatechin-3-gallate. Cancer Research, 66, 2500–2505.PubMedGoogle Scholar
  79. 79.
    Kaufmann, R., Henklein, P., Henklein, P., & Settmacher, U. (2009). Green tea polyphenol epigallocatechin-3-gallate inhibits thrombin-induced hepatocellular carcinoma cell invasion and p42/p44-MAPKinase activation. Oncology Reports, 21, 1261–1267.PubMedGoogle Scholar
  80. 80.
    Lu, L., Liu, H. M., & Tang, W. X. (2007). Effect of epigallocatechin-3-gallate on the invasiveness of hepatocarcinoma cells in vitro. Zhonghua Gan Zang Bing Za Zhi, 15, 825–827.PubMedGoogle Scholar
  81. 81.
    Lee, S. J., Lee, K. W., Hur, H. J., Chun, J. Y., Kim, S. Y., & Lee, H. J. (2007). Phenolic phytochemicals derived from red pine (Pinus densiflora) inhibit the invasion and migration of SK-Hep-1 human hepatocellular carcinoma cells. Annals of the New York Academy of Sciences, 1095, 536–544.PubMedGoogle Scholar
  82. 82.
    Zhen, M. C., Huang, X. H., Wang, Q., Sun, K., Liu, Y. J., Li, W., Zhang, L. J., Cao, L. Q., & Chen, X. L. (2006). Green tea polyphenol epigallocatechin-3-gallate suppresses rat hepatic stellate cell invasion by inhibition of MMP-2 expression and its activation. Acta Pharmacologica Sinica, 27, 1600–1607.PubMedGoogle Scholar
  83. 83.
    Zhang, G., Miura, Y., & Yagasaki, K. (2000). Suppression of adhesion and invasion of hepatoma cells in culture by tea compounds through antioxidative activity. Cancer Letters, 159, 169–173.PubMedGoogle Scholar
  84. 84.
    Zhang, G., Miura, Y., & Yagasaki, K. (2001). Inhibition of hepatoma cell invasion beneath mesothelial-cell monolayer by sera from tea- and related component-treated rats and their modes of action. Cytotechnology, 36, 187–193.PubMedGoogle Scholar
  85. 85.
    Yang, J., Wei, D., & Liu, J. (2005). Repressions of MMP-9 expression and NF-kappa B localization are involved in inhibition of lung carcinoma 95-D cell invasion by (−)-epigallocatechin-3-gallate. Biomedicine & Pharmacotherapy, 59, 98–103.Google Scholar
  86. 86.
    Hazgui, S., Bonnomet, A., Nawrocki-Raby, B., Milliot, M., Terryn, C., Cutrona, J., Polette, M., Birembaut, P., & Zahm, J. M. (2008). Epigallocatechin-3-gallate (EGCG) inhibits the migratory behavior of tumor bronchial epithelial cells. Respiratory Research, 9, 33.PubMedGoogle Scholar
  87. 87.
    Belguise, K., Guo, S., & Sonenshein, G. E. (2007). Activation of FOXO3a by the green tea polyphenol epigallocatechin-3-gallate induces estrogen receptor alpha expression reversing invasive phenotype of breast cancer cells. Cancer Research, 67, 5763–5770.PubMedGoogle Scholar
  88. 88.
    Thangapazham, R. L., Passi, N., & Maheshwari, R. K. (2007). Green tea polyphenol and epigallocatechin gallate induce apoptosis and inhibit invasion in human breast cancer cells. Cancer Biology & Therapy, 6, 1938–1943.Google Scholar
  89. 89.
    Sen, T., & Chatterjee, A. (2010). Epigallocatechin-3-gallate (EGCG) downregulates EGF-induced MMP-9 in breast cancer cells: Involvement of integrin receptor α5β1 in the process. European Journal of Nutrition, 50, 465–478.PubMedGoogle Scholar
  90. 90.
    Slivova, V., Zaloga, G., DeMichele, S. J., Mukerji, P., Huang, Y. S., Siddiqui, R., Harvey, K., Valachovicova, T., & Sliva, D. (2005). Green tea polyphenols modulate secretion of urokinase plasminogen activator (uPA) and inhibit invasive behavior of breast cancer cells. Nutrition and Cancer, 52, 66–73.PubMedGoogle Scholar
  91. 91.
    Zhang, Y., Han, G., Fan, B., Zhou, Y., Zhou, X., Wei, L., & Zhang, J. (2009). Green tea (−)-epigallocatechin-3-gallate down-regulates VASP expression and inhibits breast cancer cell migration and invasion by attenuating Rac1 activity. European Journal of Pharmacology, 606, 172–179.PubMedGoogle Scholar
  92. 92.
    Sen, T., Moulik, S., Dutta, A., Choudhury, P. R., Banerji, A., Das, S., Roy, M., & Chatterjee, A. (2009). Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7. Life Sciences, 84, 194–204.PubMedGoogle Scholar
  93. 93.
    Kushima, Y., Iida, K., Nagaoka, Y., Kawaratani, Y., Shirahama, T., Sakaguchi, M., Baba, K., Hara, Y., & Uesato, S. (2009). Inhibitory effect of (−)-epigallocatechin and (−)-epigallocatechin gallate against heregulin beta1-induced migration/invasion of the MCF-7 breast carcinoma cell line. Biological & Pharmaceutical Bulletin, 32, 899–904.Google Scholar
  94. 94.
    Farabegoli, F., Papi, A., & Orlandi, M. (2011). (−)Epigallocatechin-3-gallate downregulates EGFR, MMP-2, MMP-9 EMMPRIN and inhibits the invasion of MCF-7 tamoxifen resistant cells. Biosciences Reports, 31, 99–108.Google Scholar
  95. 95.
    Bigelow, R. L., & Cardelli, J. A. (2006). The green tea catechins, (−)-epigallocatechin-3- gallate (EGCG) and (−)-epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells. Oncogene, 25, 1922–1930.PubMedGoogle Scholar
  96. 96.
    Vayalil, P. K., & Katiyar, S. K. (2004). Treatment of epigallocatechin-3-gallate inhibits matrix metalloproteinases-2 and -9 via inhibition of activation of mitogen-activated protein kinases, c-Jun and NF-kappaB in human prostate carcinoma DU-145 cells. Prostate, 59, 33–42.PubMedGoogle Scholar
  97. 97.
    Siddiqui, I. A., Malik, A., Adhami, V. M., Asim, M., Hafeez, B. B., Sarfaraz, S., & Mukhtar, H. (2008). Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis. Oncogene, 27, 2055–2063.PubMedGoogle Scholar
  98. 98.
    Pezzato, E., Sartor, L., Dell’Aica, I., Dittadi, R., Gion, M., Belluco, C., Lise, M., & Garbisa, S. (2004). Prostate carcinoma and green tea: PSA-triggered basement membrane degradation and MMP-2 activation are inhibited by (−) epigallocatechin-3-gallate. International Journal of Cancer, 112, 787–792.Google Scholar
  99. 99.
    Sartor, L., Pezzato, E., Donà, M., Dell’Aica, I., Calabrese, F., Morini, M., Albini, A., & Garbisa, S. (2004). Prostate carcinoma and green tea: (−)epigallocatechin-3-gallate inhibits inflammation-triggered MMP-2 activation and invasion in murine TRAMP model. International Journal of Cancer, 112, 823–829.Google Scholar
  100. 100.
    Larsen, C. A., & Dashwood, R. H. (2010). (−)-Epigallocatechin-3-gallate inhibits Met signaling, proliferation, and invasiveness in human colon cancer cells. Archives of Biochemistry and Biophysics, 501, 52–57.PubMedGoogle Scholar
  101. 101.
    Ogasawara, M., Matsunaga, T., & Suzuki, H. (2007). Differential effects of antioxidants on the in vitro invasion, growth and lung metastasis of murine colon cancer cells. Biological & Pharmaceutical Bulletin, 30, 200–204.Google Scholar
  102. 102.
    Lim, Y. C., Park, H. Y., Hwang, H. S., Kang, S. U., Pyun, J. H., Lee, M. H., Choi, E. C., & Kim, C. H. (2008). (−)-Epigallocatechin-3-gallate (EGCG) inhibits HGF-induced invasion and metastasis in hypopharyngeal carcinoma cells. Cancer Letters, 271, 140–152.PubMedGoogle Scholar
  103. 103.
    Hsu, S. D., Singh, B. B., Lewis, J. B., Borke, J. L., Dickinson, D. P., Drake, L., Caughman, G. B., & Schuster, G. S. (2002). Chemoprevention of oral cancer by green tea. General Dentistry, 50, 140–146.PubMedGoogle Scholar
  104. 104.
    Ho, Y. C., Yang, S. F., Peng, C. Y., Chou, M. Y., & Chang, Y. C. (2007). Epigallocatechin-3-gallate inhibits the invasion of human oral cancer cells and decreases the productions of matrix metalloproteinases and urokinase-plasminogen activator. Journal of Oral Pathology & Medicine, 36, 588–593.Google Scholar
  105. 105.
    Kato, K., Long, N. K., Makita, H., Toida, M., Yamashita, T., Hatakeyama, D., Hara, A., Mori, H., & Shibata, T. (2008). Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells. British Journal of Cancer, 99, 647–654.PubMedGoogle Scholar
  106. 106.
    Park, J. H., Yoon, J. H., Kim, S. A., Ahn, S. G., & Yoon, J. H. (2010). (−)-Epigallocatechin-3-gallate inhibits invasion and migration of salivary gland adenocarcinoma cells. Oncology Reports, 23, 585–590.PubMedGoogle Scholar
  107. 107.
    Kim, H. S., Kim, M. H., Jeong, M., Hwang, Y. S., Lim, S. H., Shin, B. A., Ahn, B. W., & Jung, Y. D. (2004). EGCG blocks tumor promoter-induced MMP-9 expression via suppression of MAPK and AP-1 activation in human gastric AGS cells. Anticancer Research, 24, 747–753.PubMedGoogle Scholar
  108. 108.
    Maeda-Yamamoto, M., Kawahara, H., Tahara, N., Tsuji, K., Hara, Y., & Isemura, M. (1999). Effects of tea polyphenols on the invasion and matrix metalloproteinases activities of human fibrosarcoma HT1080 cells. Journal of Agricultural and Food Chemistry, 47, 2350–2354.PubMedGoogle Scholar
  109. 109.
    Maeda-Yamamoto, M., Suzuki, N., Sawai, Y., Miyase, T., Sano, M., Hashimoto-Ohta, A., & Isemura, M. (2003). Association of suppression of extracellular signal-regulated kinase phosphorylation by epigallocatechin gallate with the reduction of matrix metalloproteinase activities in human fibrosarcoma HT1080 cells. Journal of Agricultural and Food Chemistry, 51, 1858–1863.PubMedGoogle Scholar
  110. 110.
    Garbisa, S., Sartor, L., Biggin, S., Salvato, B., Benelli, R., & Albini, A. (2001). Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate. Cancer, 91, 822–832.PubMedGoogle Scholar
  111. 111.
    Dell’Aica, I., Donà, M., Sartor, L., Pezzato, E., & Garbisa, S. (2002). (−) Epigallocatechin-3-gallate directly inhibits MT1-MMP activity, leading to accumulation of nonactivated MMP-2 at the cell surface. Laboratory Investigation, 82, 1685–1693.PubMedGoogle Scholar
  112. 112.
    Takada, M., Nakamura, Y., Koizumi, T., Toyama, H., Kamigaki, T., Suzuki, Y., Takeyama, Y., & Kuroda, Y. (2002). Suppression of human pancreatic carcinoma cell growth and invasion by epigallocatechin-3-gallate. Pancreas, 25, 45–48.PubMedGoogle Scholar
  113. 113.
    Pilorget, A., Berthet, V., Luis, J., Moghrabi, A., Annabi, B., & Béliveau, R. (2003). Medulloblastoma cell invasion is inhibited by green tea (−)epigallocatechin-3-gallate. Journal of Cellular Biochemistry, 90, 745–755.PubMedGoogle Scholar
  114. 114.
    Takada, M., Ku, Y., Habara, K., Ajiki, T., Suzuki, Y., & Kuroda, Y. (2002). Inhibitory effect of epigallocatechin-3-gallate on growth and invasion in human biliary tract carcinoma cells. World Journal of Surgery, 26, 683–686.PubMedGoogle Scholar
  115. 115.
    Fassina, G., Venè, R., Morini, M., Minghelli, S., Benelli, R., Noonan, D. M., & Albini, A. (2004). Mechanisms of inhibition of tumor angiogenesis and vascular tumor growth by epigallocatechin-3-gallate. Clinical Cancer Research, 10, 4865–4873.PubMedGoogle Scholar
  116. 116.
    Liu, J. D., Chen, S. H., Lin, C. L., Tsai, S. H., & Liang, Y. C. (2001). Inhibition of melanoma growth and metastasis by combination with (−)-epigallocatechin-3-gallate and dacarbazine in mice. Journal of Cellular Biochemistry, 83, 631–642.PubMedGoogle Scholar
  117. 117.
    Suzuki, Y., & Isemura, M. (2001). Inhibitory effect of epigallocatechin gallate on adhesion of murine melanoma cells to laminin. Cancer Letters, 173, 15–20.PubMedGoogle Scholar
  118. 118.
    Wu, Y., Lin, Y., Liu, H., & Li, J. (2008). Inhibition of invasion and up-regulation of E-cadherin expression in human malignant melanoma cell line A375 by (−)-epigallocatechin-3-gallate. Journal of Huazhong University of Science and Technology. Medical Sciences, 28, 356–359.Google Scholar
  119. 119.
    Kwak, I., Shin, Y. H., Kim, M., Cha, H. Y., Nam, H. J., Lee, B. S., Chaudhary, S. C., Pai, K. S., & Lee, J. H. (2011). Epigallocatechin-3-gallate inhibits paracrine and autocrine hepatocyte growth factor/scatter factor-induced tumor cell migration and invasion. Experimental & Molecular Medicine, 43, 111–120.Google Scholar
  120. 120.
    Messina, M., Nagata, C., & Wu, A. H. (2006). Estimated Asian adult soy protein and isoflavone intakes. Nutrition and Cancer, 55, 1–12.PubMedGoogle Scholar
  121. 121.
    Bobe, G., Sansbury, L. B., Albert, P. S., Cross, A. J., Kahle, L., Ashby, J., Slattery, M. L., Caan, B., Paskett, E., Iber, F., Kikendall, J. W., Lance, P., Daston, C., Marshall, J. R., Schatzkin, A., & Lanza, E. (2008). Dietary flavonoids and colorectal adenoma recurrence in the polyp prevention trial. Cancer Epidemiology, Biomarkers & Prevention, 17, 1344–1353.Google Scholar
  122. 122.
    Hwang, Y. W., Kim, S. Y., Jee, S. H., Kim, Y. N., & Nam, C. M. (2009). Soy food consumption and risk of prostate cancer: A meta-analysis of observational studies. Nutrition and Cancer, 61, 598–606.PubMedGoogle Scholar
  123. 123.
    Magee, P. J., & Rowland, I. R. (2004). Phyto-oestrogens, their mechanism of action: Current evidence for a role in breast and prostate cancer. British Journal of Nutrition, 91, 513–531.PubMedGoogle Scholar
  124. 124.
    Park, O. J., & Surh, Y. J. (2004). Chemopreventive potential of epigallocatechin gallate and genistein: Evidence from epidemiological and laboratory studies. Toxicology Letters, 150, 43–56.PubMedGoogle Scholar
  125. 125.
    Sarkar, F. H., & Li, Y. (2002). Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer and Metastasis Reviews, 21, 265–280.PubMedGoogle Scholar
  126. 126.
    Sarkar, F. H., & Li, Y. (2003). Soy isoflavones and cancer prevention. Cancer Investigation, 217, 44–757.Google Scholar
  127. 127.
    Gu, Y., Zhu, C. F., Iwamoto, H., & Chen, J. S. (2005). Genistein inhibits invasive potential of human hepatocellular carcinoma by altering cell cycle, apoptosis, and angiogenesis. World Journal of Gastroenterology, 11, 6512–6517.PubMedGoogle Scholar
  128. 128.
    Valachovicova, T., Slivova, V., Bergman, H., Shuherk, J., & Sliva, D. (2004). Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappaB/AP-1-dependent and -independent pathways. International Journal of Oncology, 25, 1389–1395.PubMedGoogle Scholar
  129. 129.
    Magee, P. J., McGlynn, H., & Rowland, I. R. (2004). Differential effects of isoflavones and lignans on invasiveness of MDA-MB-231 breast cancer cells in vitro. Cancer Letters, 208, 35–41.PubMedGoogle Scholar
  130. 130.
    Kousidou, O. C., Mitropoulou, T. N., Roussidis, A. E., Kletsas, D., Theocharis, A. D., & Karamanos, N. K. (2005). Genistein suppresses the invasive potential of human breast cancer cells through transcriptional regulation of metalloproteinases and their tissue inhibitors. International Journal of Oncology, 26, 1101–1109.PubMedGoogle Scholar
  131. 131.
    Hsu, E. L., Chen, N. A., Westbrook, F., Wang, R., Zhang, R., Taylor, T., & Hankinson, O. (2009). Modulation of CXCR4, CXCL12, and tumor cell invasion potential in vitro by phytochemicals. Journal of Oncology, 2009, 491985.PubMedGoogle Scholar
  132. 132.
    Shao, Z. M., Wu, J., Shen, Z. Z., & Barsky, S. H. (1998). Genistein inhibits both constitutive and EGF-stimulated invasion in ER-negative human breast carcinoma cell lines. Anticancer Research, 18, 1435–1439.PubMedGoogle Scholar
  133. 133.
    Scholar, E. M., & Toews, M. L. (1994). Inhibition of invasion of murine mammary carcinoma cells by the tyrosine kinase inhibitor genistein. Cancer Letters, 87, 159–162.PubMedGoogle Scholar
  134. 134.
    Farina, H. G., Pomies, M., Alonso, D. F., & Gomez, D. E. (2006). Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncology Reports, 16, 885–891.PubMedGoogle Scholar
  135. 135.
    Zhang, L. L., Li, L., Wu, D. P., Fan, J. H., Li, X., Wu, K. J., Wang, X. Y., & He, D. L. (2008). A novel anti-cancer effect of genistein: Reversal of epithelial mesenchymal transition in prostate cancer cells. Acta Pharmacologica Sinica, 29, 1060–1068.PubMedGoogle Scholar
  136. 136.
    Li, Y., Kucuk, O., Hussain, M., Abrams, J., Cher, M. L., & Sarkar, F. H. (2006). Antitumor and antimetastatic activities of docetaxel are enhanced by genistein through regulation of osteoprotegerin/receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/MMP-9 signaling in prostate cancer. Cancer Research, 66, 4816–4825.PubMedGoogle Scholar
  137. 137.
    El Touny, L. H., & Banerjee, P. P. (2009). Identification of a biphasic role for genistein in the regulation of prostate cancer growth and metastasis. Cancer Research, 69, 3695–3703.PubMedGoogle Scholar
  138. 138.
    Huang, X., Chen, S., Xu, L., Liu, Y., Deb, D. K., Platanias, L. C., & Bergan, R. C. (2005). Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells. Cancer Research, 65, 3470–3478.PubMedGoogle Scholar
  139. 139.
    Xu, L., & Bergan, R. C. (2006). Genistein inhibits matrix metalloproteinase type 2 activation and prostate cancer cell invasion by blocking the transforming growth factor beta-mediated activation of mitogen-activated protein kinase-activated protein kinase 2-27-kDa heat shock protein pathway. Molecular Pharmacology, 70, 869–877.PubMedGoogle Scholar
  140. 140.
    Xu, L., Ding, Y., Catalona, W. J., Yang, X. J., Anderson, W. F., Jovanovic, B., Wellman, K., Killmer, J., Huang, X., Scheidt, K. A., Montgomery, R. B., & Bergan, R. C. (2009). MEK4 function, genistein treatment, and invasion of human prostate cancer cells. Journal of the National Cancer Institute, 101, 1141–1155.PubMedGoogle Scholar
  141. 141.
    El Touny, L. H., & Banerjee, P. P. (2007). Genistein induces the metastasis suppressor kangai-1 which mediates its anti-invasive effects in TRAMP cancer cells. Biochemical and Biophysics Research Communications, 361, 169–175.Google Scholar
  142. 142.
    Yan, C., & Han, R. (1999). Protein tyrosine kinase inhibitor genistein suppresses in vitro invasion of HT1080 human fibrosarcoma cells. Zhonghua Zhong Liu Za Zhi, 21, 171–174.PubMedGoogle Scholar
  143. 143.
    Yan, C., & Han, R. (1999). Effects of genistein on invasion and matrix metalloproteinase activities of HT1080 human fibrosarcoma cells. Chinese Medical Sciences Journal, 14, 129–133.PubMedGoogle Scholar
  144. 144.
    Hölting, T., Siperstein, A. E., Clark, O. H., & Duh, Q. Y. (1995). Epidermal growth factor (EGF)- and transforming growth factor alpha-stimulated invasion and growth of follicular thyroid cancer cells can be blocked by antagonism to the EGF receptor and tyrosine kinase in vitro. European Journal of Endocrinology, 132, 229–235.PubMedGoogle Scholar
  145. 145.
    Yan, C., & Han, R. (1998). Genistein suppresses adhesion-induced protein tyrosine phosphorylation and invasion of B16-BL6 melanoma cells. Cancer Letters, 129, 117–124.PubMedGoogle Scholar
  146. 146.
    Singh, R. P., & Agarwal, R. (2002). Flavonoid antioxidant silymarin and skin cancer. Antioxidants & Redox Signaling, 4, 655–663.Google Scholar
  147. 147.
    Chu, S. C., Chiou, H. L., Chen, P. N., Yang, S. F., & Hsieh, Y. S. (2004). Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Molecular Carcinogenesis, 40, 143–149.PubMedGoogle Scholar
  148. 148.
    Chen, P. N., Hsieh, Y. S., Chiou, H. L., & Chu, S. C. (2005). Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways. Chemico-Biological Interactions, 156, 141–150.PubMedGoogle Scholar
  149. 149.
    Lee, S. O., Jeong, Y. J., Im, H. G., Kim, C. H., Chang, Y. C., & Lee, I. S. (2007). Silibinin suppresses PMA-induced MMP-9 expression by blocking the AP-1 activation via MAPK signaling pathways in MCF-7 human breast carcinoma cells. Biochemical and Biophysics Research Communications, 354, 165–171.Google Scholar
  150. 150.
    Kim, S., Choi, J. H., Lim, H. I., Lee, S. K., Kim, W. W., Kim, J. S., Kim, J. H., Choe, J. H., Yang, J. H., Nam, S. J., & Lee, J. E. (2009). Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells. Phytomedicine, 16, 573–580.PubMedGoogle Scholar
  151. 151.
    Mokhtari, M. J., Motamed, N., & Shokrgozar, M. A. (2008). Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line. Cell Biology International, 32, 888–892.PubMedGoogle Scholar
  152. 152.
    Wu, K. J., Zeng, J., Zhu, G. D., Zhang, L. L., Zhang, D., Li, L., Fan, J. H., Wang, X. Y., & He, D. L. (2009). Silibinin inhibits prostate cancer invasion, motility and migration by suppressing vimentin and MMP-2 expression. Acta Pharmacologica Sinica, 30, 1162–1168.PubMedGoogle Scholar
  153. 153.
    Wu, K., Zeng, J., Li, L., Fan, J., Zhang, D., Xue, Y., Zhu, G., Yang, L., Wang, X., & He, D. (2010). Silibinin reverses epithelial-to-mesenchymal transition in metastatic prostate cancer cells by targeting transcription factors. Oncology Reports, 23, 1545–1552.PubMedGoogle Scholar
  154. 154.
    Chen, P. N., Hsieh, Y. S., Chiang, C. L., Chiou, H. L., Yang, S. F., & Chu, S. C. (2006). Silibinin inhibits invasion of oral cancer cells by suppressing the MAPK pathway. Journal of Dental Research, 85, 220–225.PubMedGoogle Scholar
  155. 155.
    Chang, H. R., Chen, P. N., Yang, S. F., Sun, Y. S., Wu, S. W., Hung, T. W., Lian, J. D., Chu, S. C., & Hsieh, Y. S. (2011). Silibinin inhibits the invasion and migration of renal carcinoma 786-O cells in vitro, inhibits the growth of xenografts in vivo and enhances chemosensitivity to 5-fluorouracil and paclitaxel. Molecular Carcinogenesis, 50, 811–823.PubMedGoogle Scholar
  156. 156.
    Hsieh, Y. S., Chu, S. C., Yang, S. F., Chen, P. N., Liu, Y. C., & Lu, K. H. (2007). Silibinin suppresses human osteosarcoma MG-63 cell invasion by inhibiting the ERK-dependent c-Jun/AP-1 induction of MMP-2. Carcinogenesis, 28, 977–987.PubMedGoogle Scholar
  157. 157.
    Naderi, G. A., Asgary, S., Sarraf-Zadegan, N., & Shirvany, H. (2003). Anti-oxidant effect of flavonoids on the susceptibility of LDL oxidation. Molecular and Cellular Biochemistry, 246, 193–196.PubMedGoogle Scholar
  158. 158.
    Mamani-Matsuda, M. (2006). Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage inflammatory mediators. Biochemical Pharmacology, 72, 1304–1310.PubMedGoogle Scholar
  159. 159.
    Lotito, S. B., & Frei, B. (2006). Dietary flavonoids attenuate tumor necrosis factor alpha-induced adhesion molecule expression in human aortic endothelial cells. Structure–function relationships and activity after first pass metabolism. The Journal of Biological Chemistry, 281, 37102–37110.PubMedGoogle Scholar
  160. 160.
    Lin, C. W., Hou, W. C., Shen, S. C., Juan, S. H., Ko, C. H., Wang, L. M., & Chen, Y. C. (2008). Quercetin inhibition of tumor invasion via suppressing PKC delta/ERK/AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells. Carcinogenesis, 29, 1807–1815.PubMedGoogle Scholar
  161. 161.
    Phromnoi, K., Yodkeeree, S., Anuchapreeda, S., & Limtrakul, P. (2009). Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids. Acta Pharmacologica Sinica, 30, 1169–1176.PubMedGoogle Scholar
  162. 162.
    Vijayababu, M. R., Arunkumar, A., Kanagaraj, P., Venkataraman, P., Krishnamoorthy, G., & Arunakaran, J. (2006). Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3). Molecular and Cellular Biochemistry, 287, 109–116.PubMedGoogle Scholar
  163. 163.
    Senthilkumar, K., Arunkumar, R., Elumalai, P., Sharmila, G., Gunadharini, D. N., Banudevi, S., Krishnamoorthy, G., Benson, C. S., & Arunakaran, J. (2011). Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC-3). Cell Biochemistry and Function, 29, 87–95.PubMedGoogle Scholar
  164. 164.
    Labbé, D., Provençal, M., Lamy, S., Boivin, D., Gingras, D., & Béliveau, R. (2009). The flavonols quercetin, kaempferol, and myricetin inhibit hepatocyte growth factor-induced medulloblastoma cell migration. The Journal of Nutrition, 139, 646–652.PubMedGoogle Scholar
  165. 165.
    Chiu, W. T., Shen, S. C., Chow, J. M., Lin, C. W., Shia, L. T., & Chen, Y. C. (2010). Contribution of reactive oxygen species to migration/invasion of human glioblastoma cells U87 via ERK-dependent COX-2/PGE(2) activation. Neurobiology of Disease, 37, 118–129.PubMedGoogle Scholar
  166. 166.
    Zhang, F. L., Zhang, W., Chen, X. M., & Luo, R. Y. (2008). Effects of quercetin and quercetin in combination with cisplatin on adhesion, migration and invasion of HeLa cells. Zhonghua Fu Chan Ke Za Zhi, 43, 619–621.PubMedGoogle Scholar
  167. 167.
    Zhang, W., & Zhang, F. (2009). Effects of quercetin on proliferation, apoptosis, adhesion and migration, and invasion of HeLa cells. European Journal of Gynaecological Oncology, 30, 60–64.PubMedGoogle Scholar
  168. 168.
    Lin, Y. S., Tsai, P. H., Kandaswami, C. C., Cheng, C. H., Ke, F. C., Lee, P. P., Hwang, J. J., & Lee, M. T. (2011). Effects of dietary flavonoids, luteolin and quercetin on the reversal of epithelial–mesenchymal transition in A431 epidermal cancer cells. Cancer Science, 102, 1829–1839.PubMedGoogle Scholar
  169. 169.
    Caltagirone, S., Rossi, C., Poggi, A., Ranelletti, F. O., Natali, P. G., Brunetti, M., Aiello, F. B., & Piantelli, M. (2000). Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. International Journal of Cancer, 87, 595–600.Google Scholar
  170. 170.
    Zhang, X. M., Huang, S. P., & Xu, Q. (2004). Quercetin inhibits the invasion of murine melanoma B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway. Cancer Chemotherapy and Pharmacology, 53, 82–88.PubMedGoogle Scholar
  171. 171.
    Jeong, Y., Tyner, A. L., & Park, J. H. (2007). Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin. American Journal of Physiology. Gastrointestinal and Liver Physiology, 292, G66–G75.PubMedGoogle Scholar
  172. 172.
    Selvendiran, K., Koga, H., Ueno, T., Yoshida, T., Maeyama, M., Torimura, T., Yano, H., Kojiro, M., & Sata, M. (2006). Luteolin promotes degradation in signal transducer and activator of transcription 3 in human hepatoma cells: An implication for the antitumor potential of flavonoids. Cancer Research, 66, 4826–4834.PubMedGoogle Scholar
  173. 173.
    Lee, W. J., Wu, L. F., Chen, W. K., Wang, C. J., & Tseng, T. H. (2006). Inhibitory effect of luteolin on hepatocyte growth factor/scatter factor-induced HepG2 cell invasion involving both MAPK/ERKs and PI3K-Akt pathways. Chemico-Biological Interactions, 160, 123–133.PubMedGoogle Scholar
  174. 174.
    Attoub, S., Hassan, A. H., Vanhoecke, B., Iratni, R., Takahashi, T., Gaben, A. M., Bracke, M., Awad, S., John, A., Kamalboor, H. A., Al Sultan, M. A., Arafat, K., Gespach, C., & Petroianu, G. (2011). Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells. European Journal of Pharmacology, 651, 18–25.PubMedGoogle Scholar
  175. 175.
    Lansky, E. P., Harrison, G., Froom, P., & Jiang, W. G. (2005). Pomegranate (Punica granatum) pure chemicals show possible synergistic inhibition of human PC-3 prostate cancer cell invasion across Matrigel. Investigational New Drugs, 23, 121–122.PubMedGoogle Scholar
  176. 176.
    Zhou, Q., Yan, B., Hu, X., Li, X. B., Zhang, J., & Fang, J. (2009). Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin. Molecular Cancer Therapeutics, 8, 1684–1691.PubMedGoogle Scholar
  177. 177.
    Lin, C. W., Shen, S. C., Chien, C. C., Yang, L. Y., Shia, L. T., & Chen, Y. C. (2010). 12-O-tetradecanoylphorbol-13-acetate-induced invasion/migration of glioblastoma cells through activating PKC alpha/ERK/NF-kappaB-dependent MMP-9 expression. Journal of Cellular Physiology, 225, 472–481.PubMedGoogle Scholar
  178. 178.
    Ross, J. A., & Kasum, C. M. (2002). Dietary flavonoids: Bioavailability, metabolic effects, and safety. Annual Review of Nutrition, 22, 19–34.PubMedGoogle Scholar
  179. 179.
    Gupta, S., Afaq, F., & Mukhtar, H. (2001). Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells. Biochemical and Biophysics Research Communications, 287, 914–920.Google Scholar
  180. 180.
    Wang, W., Heideman, L., Chung, C. S., Pelling, J. C., Koehler, K. J., & Birt, D. F. (2000). Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines. Molecular Carcinogenesis, 28, 102–110.PubMedGoogle Scholar
  181. 181.
    Way, T. D., Kao, M. C., & Lin, J. K. (2004). Apigenin induces apoptosis through proteasomal degradation of HER2/neu in HER2/neu-overexpressing breast cancer cells via the phosphatidylinositol 3-kinase/Akt-dependent pathway. The Journal of Biological Chemistry, 279, 4479–4489.PubMedGoogle Scholar
  182. 182.
    Zheng, P. W., Chiang, L. C., & Lin, C. C. (2005). Apigenin induced apoptosis through p53-dependent pathway in human cervical carcinoma cells. Life Sciences, 76, 1367–1379.PubMedGoogle Scholar
  183. 183.
    Czyz, J., Madeja, Z., Irmer, U., Korohoda, W., & Hülser, D. F. (2005). Flavonoid apigenin inhibits motility and invasiveness of carcinoma cells in vitro. International Journal of Cancer, 114, 12–18.Google Scholar
  184. 184.
    Lindenmeyer, F., Li, H., Menashi, S., Soria, C., & Lu, H. (2001). Apigenin acts on the tumor cell invasion process and regulates protease production. Nutrition and Cancer, 39, 139–147.PubMedGoogle Scholar
  185. 185.
    Lee, W. J., Chen, W. K., Wang, C. J., Lin, W. L., & Tseng, T. H. (2008). Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and beta 4 integrin function in MDA-MB-231 breast cancer cells. Toxicology and Applied Pharmacology, 226, 178–191.PubMedGoogle Scholar
  186. 186.
    Franzen, C. A., Amargo, E., Todorović, V., Desai, B. V., Huda, S., Mirzoeva, S., Chiu, K., Grzybowski, B. A., Chew, T. L., Green, K. J., & Pelling, J. C. (2009). The chemopreventive bioflavonoid apigenin inhibits prostate cancer cell motility through the focal adhesion kinase/Src signaling mechanism. Cancer Prevention Research (Phila), 2, 830–841.Google Scholar
  187. 187.
    Zhu, F., Liu, X. G., & Liang, N. C. (2003). Effect of emodin and apigenin on invasion of human ovarian carcinoma HO-8910 PM cells in vitro. Ai Zheng, 22, 358–362.PubMedGoogle Scholar
  188. 188.
    Hu, X. W., Meng, D., & Fang, J. (2008). Apigenin inhibited migration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase. Carcinogenesis, 29, 2369–2376.PubMedGoogle Scholar
  189. 189.
    Noh, H. J., Sung, E. G., Kim, J. Y., Lee, T. J., & Song, I. H. (2010). Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by apigenin via the inhibition of p38 mitogen-activated protein kinase-dependent matrix metalloproteinase-9 expression. Oncology Reports, 24, 277–283.PubMedGoogle Scholar
  190. 190.
    Maggiolini, M., Recchia, A. G., Bonofiglio, D., Catalano, S., Vivacqua, A., Carpino, A., Rago, V., Rossi, R., & Andò, S. (2005). The red wine phenolics piceatannol and myricetin act as agonists for estrogen receptor in human breast cancer cells. Journal of Molecular Endocrinology, 35, 269–281.PubMedGoogle Scholar
  191. 191.
    Nöthlings, U., Murphy, S. P., Wilkens, L. R., Henderson, B. E., & Kolonel, L. N. (2007). Flavonols and pancreatic cancer risk: The multiethnic cohort study. American Journal of Epidemiology, 166, 924–931.PubMedGoogle Scholar
  192. 192.
    Shih, Y. W., Wu, P. F., Lee, Y. C., Shi, M. D., & Chiang, T. A. (2009). Myricetin suppresses invasion and migration of human lung adenocarcinoma A549 cells: Possible mediation by blocking the ERK signaling pathway. Journal of Agricultural and Food Chemistry, 57, 3490–3499.PubMedGoogle Scholar
  193. 193.
    Ko, C. H., Shen, S. C., Lee, T. J., & Chen, Y. C. (2005). Myricetin inhibits matrix metalloproteinase 2 protein expression and enzyme activity in colorectal carcinoma cells. Molecular Cancer Therapeutics, 4, 281–290.PubMedGoogle Scholar
  194. 194.
    Kawaii, S., Tomono, Y., Katase, E., Ogawa, K., & Yano, M. (1999). Antiproliferative activity of flavonoids on several cancer cell lines. Bioscience, Biotechnology, and Biochemistry, 63, 896–899.PubMedGoogle Scholar
  195. 195.
    Bracke, M., Vyncke, B., Opdenakker, G., Foidart, J. M., de Pestel, G., & Mareel, M. (1991). Effects of catechins and citrus flavonoids on invasion in vitro. Clinical & Experimental Metastasis, 9, 13–25.Google Scholar
  196. 196.
    Mareel, M. M., & De Mets, M. (1989). Anti-invasive activities of experimental chemotherapeutic agents. Critical Reviews in Oncology/Haematology, 9, 263–303.Google Scholar
  197. 197.
    Brack, M. E., Boterberg, T., Depypere, H. T., Stove, C., Leclercq, G., & Mareel, M. M. (2002). The citrus methoxyflavone tangeretin affects human cell–cell interactions. Advances in Experimental Medicine and Biology, 505, 135–139.PubMedGoogle Scholar
  198. 198.
    Rooprai, H. K., Kandanearatchi, A., Maidment, S. L., Christidou, M., Trillo-Pazos, G., Dexter, D. T., Rucklidge, G. J., Widmer, W., & Pilkington, G. J. (2001). Evaluation of the effects of swainsonine, captopril, tangeretin and nobiletin on the biological behaviour of brain tumour cells in vitro. Neuropathology and Applied Neurobiology, 27, 29–39.PubMedGoogle Scholar
  199. 199.
    Martínez Conesa, C., Vicente Ortega, V., Yáñez Gascón, M. J., Alcaraz Baños, M., Canteras Jordana, M., Benavente-García, O., & Castillo, J. (2005). Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and diosmin. Journal of Agricultural and Food Chemistry, 53, 6791–6797.PubMedGoogle Scholar
  200. 200.
    Park, J. S., Rho, H. S., Kim, D. H., & Chang, I. S. (2006). Enzymatic preparation of kaempferol from green tea seed and its antioxidant activity. Journal of Agricultural and Food Chemistry, 54, 2951–2956.PubMedGoogle Scholar
  201. 201.
    Calderon-Montaño, J. M., Burgos-Moron, E., Perez-Guerrero, C., & Lopez-Lazaro, M. (2011). A review on the dietary flavonoid kaempferol. Mini Reviews in Medicinal Chemistry, 11, 298–344.PubMedGoogle Scholar
  202. 202.
    Shen, S. C., Lin, C. W., Lee, H. M., Chien, L. L., & Chen, Y. C. (2006). Lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate induction of migration and invasion of glioma cells in vitro and in vivo: Differential inhibitory effects of flavonoids. Neuroscience, 140, 477–489.PubMedGoogle Scholar
  203. 203.
    Lee, E. J., Kim, S. Y., Hyun, J. W., Min, S. W., Kim, D. H., & Kim, H. S. (2010). Glycitein inhibits glioma cell invasion through down-regulation of MMP-3 and MMP-9 gene expression. Chemico-Biological Interactions, 185, 18–24.PubMedGoogle Scholar
  204. 204.
    Park, S. Y., Lim, S. S., Kim, J. K., Kang, I. J., Kim, J. S., Lee, C., Kim, J., & Park, J. H. (2010). Hexane-ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells. British Journal of Nutrition, 104, 1–11.Google Scholar
  205. 205.
    Kahkonen, M. P., & Heinonen, M. (2003). Antioxidant activity of anthocyanins and their aglycons. Journal of Agricultural and Food Chemistry, 51, 628–633.PubMedGoogle Scholar
  206. 206.
    Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W., Fong, H. H., Farnsworth, N. R., Kinghorn, A. D., Mehta, R. G., Moon, R. C., & Pezzuto, J. M. (1997). Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 275, 218–220.PubMedGoogle Scholar
  207. 207.
    Middleton, E., Jr., Kandaswami, C., & Theoharides, T. C. (2000). The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacological Reviews, 52, 673–751.PubMedGoogle Scholar
  208. 208.
    Katsube, N., Iwashita, K., Tsushida, T., Yamaki, K., & Kobori, M. (2003). Induction of apoptosis in cancer cells by Bilberry (Vaccinium myrtillus) and the anthocyanins. Journal of Agricultural and Food Chemistry, 51, 68–75.PubMedGoogle Scholar
  209. 209.
    Bagchi, D., Sen, C. K., Bagchi, M., & Atala, M. (2004). Anti-angiogenic, antioxidant, and anti-carcinogenic properties of a novel anthocyanin-rich berry extract formula. Biochemistry (Mosc), 69, 75–80.Google Scholar
  210. 210.
    Nagase, H., Sasaki, K., Kito, H., Haga, A., & Sato, T. (1998). Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT-1080 invasiveness in vitro. Planta Medica, 64, 216–219.PubMedGoogle Scholar
  211. 211.
    Chen, P. N., Chu, S. C., Chiou, H. L., Kuo, W. H., Chiang, C. L., & Hsieh, Y. S. (2006). Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Letters, 235, 248–259.PubMedGoogle Scholar
  212. 212.
    Shin, D. Y., Ryu, C. H., Lee, W. S., Kim, D. C., Kim, S. H., Hah, Y. S., Lee, S. J., Shin, S. C., Kang, H. S., & Choi, Y. H. (2009). Induction of apoptosis and inhibition of invasion in human hepatoma cells by anthocyanins from meoru. Annals of the New York Academy of Sciences, 1171, 137–148.PubMedGoogle Scholar
  213. 213.
    Shin, D. Y., Lee, W. S., Kim, S. H., Kim, M. J., Yun, J. W., Lu, J. N., Lee, S. J., Tsoy, I., Kim, H. J., Ryu, C. H., Kim, G. Y., Kang, H. S., Shin, S. C., & Choi, Y. H. (2009). Anti-invasive activity of anthocyanins isolated from Vitis coignetiae in human hepatocarcinoma cells. Journal of Medicinal Food, 12, 967–972.PubMedGoogle Scholar
  214. 214.
    Ho, M. L., Chen, P. N., Chu, S. C., Kuo, D. Y., Kuo, W. H., Chen, J. Y., & Hsieh, Y. S. (2010). Peonidin 3-glucoside inhibits lung cancer metastasis by downregulation of proteinases activities and MAPK pathway. Nutrition and Cancer, 62, 505–516.PubMedGoogle Scholar
  215. 215.
    Syed, D. N., Afaq, F., Sarfaraz, S., Khan, N., Kedlaya, R., Setaluri, V., & Mukhtar, H. (2008). Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation. Toxicology and Applied Pharmacology, 231, 52–60.PubMedGoogle Scholar
  216. 216.
    Xu, M., Bower, K. A., Wang, S., Frank, J. A., Chen, G., Ding, M., Wang, S., Shi, X., Ke, Z., & Luo, J. (2010). Cyanidin-3-glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2. Molecular Cancer, 9, 285.PubMedGoogle Scholar
  217. 217.
    Matchett, M. D., MacKinnon, S. L., Sweeney, M. I., Gottschall-Pass, K. T., & Hurta, R. A. (2005). Blueberry flavonoids inhibit matrix metalloproteinase activity in DU145 human prostate cancer cells. Biochemistry and Cell Biology, 83, 637–643.PubMedGoogle Scholar
  218. 218.
    Matchett, M. D., MacKinnon, S. L., Sweeney, M. I., Gottschall-Pass, K. T., & Hurta, R. A. (2006). Inhibition of matrix metalloproteinase activity in DU145 human prostate cancer cells by flavonoids from lowbush blueberry (Vaccinium angustifolium): Possible roles for protein kinase C and mitogen-activated protein-kinase-mediated events. The Journal of Nutritional Biochemistry, 17, 117–125.PubMedGoogle Scholar
  219. 219.
    Yun, J. W., Lee, W. S., Kim, M. J., Lu, J. N., Kang, M. H., Kim, H. G., Kim, D. C., Choi, E. J., Choi, J. Y., Kim, H. G., Lee, Y. K., Ryu, C. H., Kim, G., Choi, Y. H., Park, O. J., & Shin, S. C. (2010). Characterization of a profile of the anthocyanins isolated from Vitis coignetiae Pulliat and their anti-invasive activity on HT-29 human colon cancer cells. Food and Chemical Toxicology, 48, 903–909.PubMedGoogle Scholar
  220. 220.
    Shin, D. Y., Lu, J. N., Kim, G. Y., Jung, J. M., Kang, H. S., Lee, W. S., & Choi, Y. H. (2011). Anti-invasive activities of anthocyanins through modulation of tight junctions and suppression of matrix metalloproteinase activities in HCT-116 human colon carcinoma cells. Oncology Reports, 25, 567–572.PubMedGoogle Scholar
  221. 221.
    Chen, P. N., Kuo, W. H., Chiang, C. L., Chiou, H. L., Hsieh, Y. S., & Chu, S. C. (2006). Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression. Chemico-Biological Interactions, 163, 218–229.PubMedGoogle Scholar
  222. 222.
    Lamy, S., Lafleur, R., Bédard, V., Moghrabi, A., Barrette, S., Gingras, D., & Béliveau, R. (2007). Anthocyanidins inhibit migration of glioblastoma cells: Structure–activity relationship and involvement of the plasminolytic system. Journal of Cellular Biochemistry, 100, 100–111.PubMedGoogle Scholar
  223. 223.
    Shankar, S., Ganapathy, S., Hingorani, S. R., & Srivastava, R. K. (2008). EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Frontiers in Bioscience, 13, 440–452.PubMedGoogle Scholar
  224. 224.
    Pfeffer, U., Ferrari, N., Dell’Eva, R., Indraccolo, S., Morini, M., Noonan, D. M., & Albini, A. (2005). Molecular mechanisms of action of angiopreventive anti-oxidants on endothelial cells: Microarray gene expression analyses. Mutation Research, 591, 198–211.PubMedGoogle Scholar
  225. 225.
    Yamakawa, S., Asai, T., Uchida, T., Matsukawa, M., Akizawa, T., & Oku, N. (2004). (−)-Epigallocatechin gallate inhibits membrane-type 1 matrix metalloproteinase, MT1-MMP, and tumor angiogenesis. Cancer Letters, 210, 47–55.PubMedGoogle Scholar
  226. 226.
    Iishi, H., Tatsuta, M., Baba, M., Yano, H., Sakai, N., & Akedo, H. (2000). Genistein attenuates peritoneal metastasis of azoxymethane-induced intestinal adenocarcinomas in Wistar rats. International Journal of Cancer, 86, 416–420.Google Scholar
  227. 227.
    Lakshman, M., Xu, L., Ananthanarayanan, V., Cooper, J., Takimoto, C. H., Helenowski, I., Pelling, J. C., & Bergan, R. C. (2008). Dietary genistein inhibits metastasis of human prostate cancer in mice. Cancer Research, 68, 2024–2032.PubMedGoogle Scholar
  228. 228.
    Singh, A. V., Franke, A. A., Blackburn, G. L., & Zhou, J. R. (2006). Soy phytochemicals prevent orthotopic growth and metastasis of bladder cancer in mice by alterations of cancer cell proliferation and apoptosis and tumor angiogenesis. Cancer Research, 66, 1851–1858.PubMedGoogle Scholar
  229. 229.
    Singh, R. P., Raina, K., Sharma, G., & Agarwal, R. (2008). Silibinin inhibits established prostate tumor growth, progression, invasion, and metastasis and suppresses tumor angiogenesis and epithelial–mesenchymal transition in transgenic adenocarcinoma of the mouse prostate model mice. Clinical Cancer Research, 14, 7773–7780.PubMedGoogle Scholar
  230. 230.
    Raina, K., Rajamanickam, S., Singh, R. P., Deep, G., Chittezhath, M., & Agarwal, R. (2008). Stage-specific inhibitory effects and associated mechanisms of silibinin on tumor progression and metastasis in transgenic adenocarcinoma of the mouse prostate model. Cancer Research, 68, 6822–6830.PubMedGoogle Scholar
  231. 231.
    Singh, R. P., Dhanalakshmi, S., Agarwal, C., & Agarwal, R. (2005). Silibinin strongly inhibits growth and survival of human endothelial cells via cell cycle arrest and downregulation of survivin, Akt and NF-kappaB: Implications for angioprevention and antiangiogenic therapy. Oncogene, 24, 1188–1202.PubMedGoogle Scholar
  232. 232.
    Devipriya, S., Ganapathy, V., & Shyamaladevi, C. S. (2006). Suppression of tumor growth and invasion in 9,10 dimethyl benz(a) anthracene induced mammary carcinoma by the plant bioflavonoid quercetin. Chemico-Biological Interactions, 162, 106–113.PubMedGoogle Scholar
  233. 233.
    Tan, W. F., Lin, L. P., Li, M. H., Zhang, Y. X., Tong, Y. G., Xiao, D., & Ding, J. (2003). Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential. European Journal of Pharmacology, 459, 255–262.PubMedGoogle Scholar
  234. 234.
    Tatsuta, A., Iishi, H., Baba, M., Yano, H., Murata, K., Mukai, M., & Akedo, H. (2000). Suppression by apigenin of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats. Clinical & Experimental Metastasis, 18, 657–662.Google Scholar
  235. 235.
    Fang, J., Zhou, Q., Liu, L. Z., Xia, C., Hu, X., Shi, X., & Jiang, B. H. (2007). Apigenin inhibits tumor angiogenesis through decreasing HIF-1alphaand VEGF expression. Carcinogenesis, 28, 858–864.PubMedGoogle Scholar
  236. 236.
    Lentini, A., Forni, C., Provenzano, B., & Beninati, S. (2007). Enhancement of transglutaminase activity and polyamine depletion in B16-F10 melanoma cells by flavonoids naringenin and hesperitin correlate to reduction of the in vivo metastatic potential. Amino Acids, 32, 95–100.PubMedGoogle Scholar
  237. 237.
    Ding, M., Feng, R., Wang, S. Y., Bowman, L., Lu, Y., Qian, Y., Castranova, V., Jiang, B. H., & Shi, X. (2006). Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. The Journal of Biological Chemistry, 281, 17359–17368.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Graduate Institute of Applied Science of LivingTainan University of TechnologyTainan CityTaiwan
  2. 2.Department of Food Science and BiotechnologyNational Chung Hsing UniversityTaichungTaiwan

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