The isoflavone metabolite 6-methoxyequol inhibits angiogenesis and suppresses tumor growth

Molecular Cancer

Volumn 11, Issue , 2012, Pages

  Bellou, Sofia ^a,b   Karali, Evdoxia ^b,f   Bagli, Eleni ^b   Al Maharik, Nawaf ^c   Morbidelli, Lucia ^d   Ziche, Marina ^d   Adlercreutz, Herman ^e   Murphy, Carol ^b   Fotsis, Theodore ^b,f  

^a UNIVERSITY OF WESTERN MACEDONIA   (Greece)

^b INSTITUTE OF COMPUTER SCIENCE   (Greece)

^c UNIVERSITY OF ST ANDREWS   (United Kingdom)

^d UNIVERSITY OF SIENA   (Italy)

^e UNIVERSITY OF HELSINKI   (Finland)

^f UNIVERSITY OF IOANNINA   (Greece)

Author keywords

A 431 xenograft; Angiogenesis; Mapk; Phytoestrogen; Vegf

Indexed keywords

6 METHOXYEQUOL; ANGIOGENESIS INHIBITOR; FIBROBLAST GROWTH FACTOR 2; ISOFLAVONE; MITOGEN ACTIVATED PROTEIN KINASE; PHYTOESTROGEN; SYNAPTOPHYSIN; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BRAIN CAPILLARY ENDOTHELIAL CELL; CANCER INHIBITION; CELL LINE; CELL MIGRATION; CELL PROLIFERATION; CELL STRAIN LNCAP; CELL STRAIN MCF 7; CELL STRAIN T 24; CELL SURVIVAL; ENDOTHELIUM CELL; HELA CELL; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; PROTEIN PHOSPHORYLATION; TUMOR XENOGRAFT; UMBILICAL VEIN ENDOTHELIAL CELL;

ANGIOGENESIS INHIBITORS; ANIMALS; CATTLE; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; CELL SURVIVAL; DRUG SCREENING ASSAYS, ANTITUMOR; EQUOL; FEMALE; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; ISOFLAVONES; MAP KINASE SIGNALING SYSTEM; MICE; MICE, NUDE; MITOSIS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; TUMOR BURDEN; VASCULAR ENDOTHELIAL GROWTH FACTOR A; XENOGRAFT MODEL ANTITUMOR ASSAYS;

BOVINAE;

EID: 84860808550     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/1476-4598-11-35     Document Type: Article

References (34)

1. Grothey A, Galanis E. Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nat Rev Clin Oncol 2009, 6(9):507-18. 10.1038/nrclinonc.2009.110, 19636328.
2. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003, 9(6):669-76. 10.1038/nm0603-669, 12778165.
3. Tozer GM, et al. Blood vessel maturation and response to vascular-disrupting therapy in single vascular endothelial growth factor-A isoform-producing tumors. Cancer Res 2008, 68(7):2301-11. 10.1158/0008-5472.CAN-07-2011, 18381437.
4. Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 2002, 20(21):4368-80. 10.1200/JCO.2002.10.088, 12409337.
5. Takahashi T, et al. A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO J 2001, 20(11):2768-78. 10.1093/emboj/20.11.2768, 125481, 11387210.
6. Kobayashi M, et al. MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration. EMBO J 2006, 25(4):713-26. 10.1038/sj.emboj.7600973, 1383554, 16456544.
7. Bellou S, et al. VEGF Auto-regulates its Proliferative and Migratory ERK1/2 and p38 Cascades by Enhancing the Expression of DUSP1 and DUSP5 Phosphatases in Endothelial Cells. Am J Physiol Cell Physiol 2009, 297(6):1477-1489.
8. Fotsis T, et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci U S A 1993, 90(7):2690-4. 10.1073/pnas.90.7.2690, 46161, 7681986.
9. Fotsis T, et al. Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res 1997, 57(14):2916-21.
10. Bagli E, et al. Luteolin inhibits vascular endothelial growth factor-induced angiogenesis; inhibition of endothelial cell survival and proliferation by targeting phosphatidylinositol 3'-kinase activity. Cancer Res 2004, 64(21):7936-46. 10.1158/0008-5472.CAN-03-3104, 15520200.
11. Gerber HP, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 1998, 273(46):30336-43. 10.1074/jbc.273.46.30336, 9804796.
12. Lamalice L, et al. Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38. Oncogene 2004, 23(2):434-45. 10.1038/sj.onc.1207034, 14724572.
13. Wang JK, et al. Broadly expressed SNT-like proteins link FGF receptor stimulation to activators of Ras. Oncogene 1996, 13(4):721-9.
14. Kouhara H, et al. A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway. Cell 1997, 89(5):693-702. 10.1016/S0092-8674(00)80252-4, 9182757.
15. Gomez AR, et al. Conserved cross-interactions in Drosophila and Xenopus between Ras/MAPK signaling and the dual-specificity phosphatase MKP3. Dev Dyn 2005, 232(3):695-708. 10.1002/dvdy.20227, 15704110.
16. Kucharska A, et al. Regulation of the inducible nuclear dual-specificity phosphatase DUSP5 by ERK MAPK. Cell Signal 2009, 21(12):1794-1805. 10.1016/j.cellsig.2009.07.015, 19666109.
17. Hu JH, et al. Feedback control of MKP-1 expression by p38. Cell Signal 2007, 19(2):393-400. 10.1016/j.cellsig.2006.07.010, 16978838.
18. McMullen ME, et al. Activation of p38 has opposing effects on the proliferation and migration of endothelial cells. J Biol Chem 2005, 280(22):20995-1003. 10.1074/jbc.M407060200, 15790570.
19. Myoken Y, et al. Vascular endothelial cell growth factor (VEGF) produced by A-431 human epidermoid carcinoma cells and identification of VEGF membrane binding sites. Proc Natl Acad Sci U S A 1991, 88(13):5819-23. 10.1073/pnas.88.13.5819, 51969, 1712106.
20. Heinonen SM, et al. Studies of the in vitro intestinal metabolism of isoflavones aid in the identification of their urinary metabolites. J Agric Food Chem 2004, 52(9):2640-6. 10.1021/jf030681s, 15113171.
21. Xu X, et al. Bioavailability of soybean isoflavones depends upon gut microflora in women. J Nutr 1995, 125(9):2307-15.
22. Borsi L, et al. Selective targeted delivery of TNFalpha to tumor blood vessels. Blood 2003, 102(13):4384-92. 10.1182/blood-2003-04-1039, 12933583.
23. Pini A, et al. Design and use of a phage display library. Human antibodies with subnanomolar affinity against a marker of angiogenesis eluted from a two-dimensional gel. J Biol Chem 1998, 273(34):21769-76. 10.1074/jbc.273.34.21769, 9705314.
24. Heinonen SM, et al. Metabolism of the soy isoflavones daidzein, genistein and glycitein in human subjects. Identification of new metabolites having an intact isoflavonoid skeleton. J Steroid Biochem Mol Biol 2003, 87(4-5):285-99.
25. Heinonen SM, Wahala K, Adlercreutz H. Identification of urinary metabolites of the red clover isoflavones formononetin and biochanin A in human subjects. J Agric Food Chem 2004, 52(22):6802-9. 10.1021/jf0492767, 15506819.
26. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 473(7347):298-307.
27. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev 1997, 18(1):4-25. 10.1210/er.18.1.4, 9034784.
28. Kleinman HK, Martin GR. Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol 2005, 15(5):378-86. 10.1016/j.semcancer.2005.05.004, 15975825.
29. Rousseau S, et al. p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells. Oncogene 1997, 15(18):2169-77. 10.1038/sj.onc.1201380, 9393975.
30. Doanes AM, et al. VEGF stimulates MAPK through a pathway that is unique for receptor tyrosine kinases. Biochem Biophys Res Commun 1999, 255(2):545-8. 10.1006/bbrc.1999.0227, 10049745.
31. Graziani Y, Erikson E, Erikson RL. The effect of quercetin on the phosphorylation activity of the Rous sarcoma virus transforming gene product in vitro and in vivo. Eur J Biochem 1983, 135(3):583-9. 10.1111/j.1432-1033.1983.tb07692.x, 6311542.
32. Cunningham BD, et al. Synthesis and biological evaluation of a series of flavones designed as inhibitors of protein tyrosine kinases. Anticancer Drug Des 1992, 7(5):365-84.
33. Ribatti D. Novel angiogenesis inhibitors: addressing the issue of redundancy in the angiogenic signaling pathway. Cancer Treat Rev 2011, 37(5):344-52. 10.1016/j.ctrv.2011.02.002, 21435792.
34. Grepin R, Pages G. Molecular mechanisms of resistance to tumour anti-angiogenic strategies. J Oncol 2010, 2010:835680. 2836176, 20224655.