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Cancer and Metastasis Reviews

Erschienen in:

01.06.2012 | NON-THEMATIC REVIEW

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

verfasst von: Chia-Jui Weng, Gow-Chin Yen

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 1-2/2012

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Abstract

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.

Weiss, L. (1990). Metastatic inefficiency. Advances in Cancer Research, 54, 159–211.PubMed

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.PubMed

Condeelis, J., & Segall, J. E. (2003). Intravital imaging of cell movement in tumours. Nature Reviews. Cancer, 3, 921–930.PubMed

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.

Shahidi, F. (2000). Antioxidants in food and food antioxidants. Die Nahrung, 44, 158–163.PubMed

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.

Cook, N. C., & Samman, S. (1996). Flavonoids—chemistry, metabolism, cardioprotective effects, and dietary sources. The Journal of Nutritional Biochemistry, 7, 66–76.

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.PubMed

Sliva, D. (2008). Suppression of cancer invasiveness by dietary compounds. Mini Reviews in Medicinal Chemistry, 8, 677–688.PubMed

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.PubMed

11.

Christofori, G. (2006). New signals from the invasive front. Nature, 441, 444–450.PubMed

12.

Thiery, J. P. (2002). Epithelial–mesenchymal transitions in tumour progression. Nature Reviews. Cancer, 2, 442–454.PubMed

13.

Yang, J., & Weinberg, R. A. (2008). Epithelial–mesenchymal transition: At the crossroads of development and tumor metastasis. Developmental Cell, 14, 818–829.PubMed

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

31.

Myatt, S. S., & Lam, E. W. (2007). The emerging roles of forkhead box (Fox) proteins in cancer. Nature Reviews. Cancer, 7, 847–859.PubMed

32.

Humphries, M. J. (2000). Integrin structure. Biochemical Society Transactions, 28, 311–339.PubMed

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.PubMed

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.PubMed

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.PubMed

36.

Sahai, E. (2007). Illuminating the metastatic process. Nature Reviews. Cancer, 7, 737–749.PubMed

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.PubMed

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.PubMed

39.

Kleiner, D. E., & Stetler-Stevenson, W. G. (1999). Matrix metalloproteinases and metastasis. Cancer Chemotherapy and Pharmacology, 43, S41–S51.

40.

Westermarck, J., & Kahari, V. M. (1999). Regulation of matrix metalloproteinase expression in tumor invasion. The FASEB Journal, 13, 781–792.

41.

Friedl, P., & Wolf, K. (2003). Tumour-cell invasion and migration: Diversity and escape mechanisms. Nature Reviews. Cancer, 3, 362–374.PubMed

42.

Rao, J. S. (2003). Molecular mechanisms of glioma invasiveness: The role of proteases. Nature Reviews. Cancer, 3, 489–501.PubMed

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

55.

Rao, A. R., Motiwala, H. G., & Karim, O. M. (2008). The discovery of prostate-specific antigen. BJU International, 101, 5–10.PubMed

56.

Lilja, H. (2003). Biology of prostate-specific antigen. Urology, 62, 27–33.PubMed

57.

Fuchs, E. (1882). Das Sarcom des Uvealtractus. In W. Braumueller (Ed.), Metastasenbildung (pp. 197–206). Vienna: Wilhelm Braumuller.

58.

Paget, S. (1889). The distribution of secondary growths in cancer of the breast. Lancet, 1, 571–573.

59.

Fidler, I. J. (2003). The pathogenesis of cancer metastasis: The ‘seed and soil’ hypothesis revisited. Nature Reviews. Cancer, 3, 453–458.PubMed

60.

Ruoslahti, E., & Rajotte, D. (2000). An address system in the vasculature of normal tissues and tumors. Annual Review of Immunology, 18, 813–827.PubMed

61.

Brown, D. M., & Metadherin, R. E. (2004). A cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell, 5, 365–374.PubMed

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.PubMed

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.PubMed

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.PubMed

65.

Bergers, G., & Benjamin, L. E. (2003). Tumorigenesis and the angiogenic switch. Nature Reviews. Cancer, 3, 401–410.PubMed

66.

Kalluri, R. (2003). Basement membranes: Structure, assembly and role in tumour angiogenesis. Nature Reviews. Cancer, 3, 422–433.PubMed

67.

Thurston, G. (2003). Role of Angiopoietins and Tie receptor tyrosine kinases in angiogenesis and lymphangiogenesis. Cell and Tissue Research, 314, 61–68.PubMed

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.PubMed

69.

Harris, A. L. (2002). Hypoxia—a key regulatory factor in tumour growth. Nature Reviews. Cancer, 2, 38–47.PubMed

70.

Sullivan, R., & Graham, C. H. (2007). Hypoxia-driven selection of the metastatic phenotype. Cancer and Metastasis Reviews, 26, 319–331.PubMed

71.

Semenza, G. L. (2003). Targeting HIF-1 for cancer therapy. Nature Reviews. Cancer, 3, 721–732.PubMed

72.

Semenza, G. L. (2007). Evaluation of HIF-1 inhibitors as anticancer agents. Drug Discovery Today, 12, 853–859.PubMed

73.

Melillo, G. (2006). Inhibiting hypoxia-inducible factor 1 for cancer therapy. Molecular Cancer Research, 4, 601–605.PubMed

74.

Steeg, P. S. (2006). Tumor metastasis: Mechanistic insights and clinical challenges. Nature Medicine, 12, 895–904.PubMed

75.

Khan, N., & Mukhtar, H. (2007). Tea polyphenols for health promotion. Life Sciences, 81, 519–533.PubMed

76.

Chacko, S. M., Thambi, P. T., Kuttan, R., & Nishigaki, I. (2010). Beneficial effects of green tea: A literature review. Chinese Medicine, 5, 13.PubMed

77.

Cao, Y., Cao, R., & Brakenhielm, E. (2002). Antiangiogenic mechanisms of diet-derived polyphenols. The Journal of Nutritional Biochemistry, 13, 380–390.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.

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.

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.PubMed

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.PubMed

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.PubMed

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.

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.

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.PubMed

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.

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

117.

Suzuki, Y., & Isemura, M. (2001). Inhibitory effect of epigallocatechin gallate on adhesion of murine melanoma cells to laminin. Cancer Letters, 173, 15–20.PubMed

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.

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.

120.

Messina, M., Nagata, C., & Wu, A. H. (2006). Estimated Asian adult soy protein and isoflavone intakes. Nutrition and Cancer, 55, 1–12.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

125.

Sarkar, F. H., & Li, Y. (2002). Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer and Metastasis Reviews, 21, 265–280.PubMed

126.

Sarkar, F. H., & Li, Y. (2003). Soy isoflavones and cancer prevention. Cancer Investigation, 217, 44–757.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

146.

Singh, R. P., & Agarwal, R. (2002). Flavonoid antioxidant silymarin and skin cancer. Antioxidants & Redox Signaling, 4, 655–663.

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

178.

Ross, J. A., & Kasum, C. M. (2002). Dietary flavonoids: Bioavailability, metabolic effects, and safety. Annual Review of Nutrition, 22, 19–34.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.

196.

Mareel, M. M., & De Mets, M. (1989). Anti-invasive activities of experimental chemotherapeutic agents. Critical Reviews in Oncology/Haematology, 9, 263–303.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.

205.

Kahkonen, M. P., & Heinonen, M. (2003). Antioxidant activity of anthocyanins and their aglycons. Journal of Agricultural and Food Chemistry, 51, 628–633.PubMed

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.PubMed

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.PubMed

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.

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.PubMed

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.PubMed

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.PubMed

Titel: Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities
verfasst von: Chia-Jui Weng
Gow-Chin Yen
Publikationsdatum: 01.06.2012
Verlag: Springer US
Erschienen in: Cancer and Metastasis Reviews / Ausgabe 1-2/2012
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-012-9347-y

Springer Medizin

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

Abstract

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Abstract

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