Angiogenesis, the formation of new blood vessels from host vasculature, is critical for tumor growth and metastases. Curcumin, a novel smallmolecular- weight compound, has been shown to inhibit carcinogenesis in different organs and the common link between these actions is its antiangiogenic effect.


Melanoma Cell Raji Cell Endothelial Cell Migration Curcumin Treatment Urokinase Plasminogen Activator 
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  1. 1.
    1. J. Folkman, Tumor angiogenesis: Therapeutic implications. New Engl J Med 285, 1182–1186 (1971).PubMedCrossRefGoogle Scholar
  2. 2.
    2. J. Folkman, Angiogenesis and apoptosis. Semin Cancer Biol 13(2), 159–167 (2003).PubMedCrossRefGoogle Scholar
  3. 3.
    3. T. P. Robinson, T. Ehlers, R. B. Hubbard IV, X. Bai, J. L. Arbiser, D. J. Goldsmith, and J. P. Bowen, Design, synthesis, and biological evaluation of angiogenesis inhibitors: Aromatic enone and dienone analogues of curcumin. Bioorg Med Chem Lett 13(1), 115–117 (2003).PubMedCrossRefGoogle Scholar
  4. 4.
    4. M. S. Furness, T. P. Robinson, T. Ehlers, R. B. Hubbard 4th, J. L. Arbiser, D. J. Goldsmith, and J. P. Bowen, Antiangiogenic agents: Studies on fumagillin and curcumin analogs. Curr Pharm Des 11, 357–373 (2005).PubMedCrossRefGoogle Scholar
  5. 5.
    5. J. Folkman and D. Hanahan, Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86, 353–364 (1996).PubMedCrossRefGoogle Scholar
  6. 6.
    6. J. L. Arbiser, M. A. Moses, C. A. Fernandez, N. Ghiso, Y. Cao, N. Klauber, D. Frank, M. Brownlee, E. Flynn, S. Parangi, H. R. Byers, and J. Folkman, Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci USA 94(3), 861–866 (1997).PubMedCrossRefGoogle Scholar
  7. 7.
    7. J. L. Arbiser, N. Klauber, R. Rohan, R. van Leeuwen, M. T. Huang, C. Fisher E. Flynn, and H. R. Byers, Curcumin is an in vivo inhibitor of angiogenesis. Mol Med 4, 376–383 (1998).PubMedGoogle Scholar
  8. 8.
    8. R. Klafer and J. L. Arbiser, Regulation of angiogenesis and tumorigenesis by signal transduction cascades: lessons from benign and malignant endothelial tumors. J Investig Dermatol Symp Proc 5(1), 79–82 (2000).CrossRefGoogle Scholar
  9. 9.
    9. G. N. Naumov, E. Bender, D. Zurakowski, S. Y. Kang, D. Sampson, E. Flynn, R. S. Watnick, O. Straume, L. A. Akslen, J. Folkman, and N. Almog, A model of human tumor dormancy: An angiogenic switch from the nonangiogenic phenotype. J Natl Cancer Inst 98(5), 316–325 (2006).PubMedCrossRefGoogle Scholar
  10. 10.
    10. R. Bianco, D. Melisi, F. Ciardiello, G. Tortora, Key cancer cell signal transduction pathways as therapeutic targerts, Eur J Cancer 42, 290–294 (2006).PubMedCrossRefGoogle Scholar
  11. 11.
    11. W. H. Chen, Y. Chen, and G. H. Cui, Effects of TNF-alpha and curcumin on the expression of VEGF in Raji and U937 cells on angiogenesis in ECV304 cells. Chin Med J (Engl) 118(24), 2052–2057 (2005).Google Scholar
  12. 12.
    12. S. Sawant, S. Aparicio, A. R. Tink, N. Lara, C. J. Barnstable, and J. Tombran-Tink, Regulation of factors controlling angiogenesis in liver development: A role for PEDF in the formation and maintenance of normal vasculature. Biochem Biophys Res Commun. 325(2), 408–413 (2004).PubMedCrossRefGoogle Scholar
  13. 13.
    13. K. Q. Hu, C. H. Yu, Y. Mineyama, J. D. McCracken, D. J. Hillebrand, and M. Hasan, Inhibited proliferation of cyclooxygenase-2 expressing human hepatoma cells by NS-398, a selective COX-2 inhibitor, Int J Oncol 22(4), 757–763 (2003).PubMedGoogle Scholar
  14. 14.
    14. F. Millanta, S. Citi, D. Della Santa, M. Porciani, and A. Poli, COX-2 expression in canine and feline invasive mammary carcinomas: Correlation with clinicopathological features and prognostic molecular markers. Breast Cancer Res Treat. 98(1), 115–120 (2006) Mar 15; [Epub ahead of print]PubMedCrossRefGoogle Scholar
  15. 15.
    15. P. Yoysungnoen, P Wirachwong, P Bhattarakosol, H. Niimi, and S. Patumraj, Effects of curcumin on tumor angiogenesis and biomarkers, COX-2 and VEGF, in hepatocellular carcinoma cell-implanted nude mice. Clin Hemorheol Microcirc 34(1–2), 109–115 (2006).PubMedGoogle Scholar
  16. 16.
    16. L. Li, F. S. Braiteh, and R. Kurzrock, Liposome-encapsulated curcumin: In vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. Cancer 104(6), 1322–1331 (2005).PubMedCrossRefGoogle Scholar
  17. 17.
    17. K. C. Kent, S. Mii, E. O. Harrington, J. D. Chang, S. Mallette, and J. A. Ware, Requirement for protein kinase C activation in basic fibroblast growth factor-induced human endothelial cell proliferation. Cir Res 77, 231–238 (1995).Google Scholar
  18. 18.
    18. B. B. Aggarwal and K. Natarajan, Tumor necrosis factor: Developments during the last decade. Eur Cytokine Netw 7, 93–124 (1996).PubMedGoogle Scholar
  19. 19.
    19. A. Noel, C. Gilles, K. Bajou, L. Devy, F. Kebers, J. M. Lewalle, et al., Emerging roles for proteinases in cancer. Invasion Metastasis 17, 221–239 (1997).PubMedGoogle Scholar
  20. 20.
    20. D. B. Rifkin, R. Mazzieri, J. S. Munger, I. Noguera, and J. Sung, Proteolytic control of growth factor availability. APMIS 107, 80–85 (1999).PubMedCrossRefGoogle Scholar
  21. 21.
    21. M. Egeblad and Z. Werb, New functions for the matrix metalloproteinases in cancer progression, Nature Rev 2, 161–174 (2002).CrossRefGoogle Scholar
  22. 22.
    22. S. S. Twining, Regulation of proteolytic activity in tissues. Crit Rev Biochem Mol Biol 29, 315–383 (1994).PubMedGoogle Scholar
  23. 23.
    23. H. Li, C. Soria, F. Griscelli, P. Opolon, J. Soria, P. Yen, C. Legrand, J. P. Vannier, D. Belin, M. Perricaudet, and H. Lu, Amino-terminal fragment of urokinase inhibits tumor cell invasion in vitro and in vivo: Respective contribution of the urokinase plasminogen activator receptor-dependent or -independent pathway. Hum Gene Ther 16(10), 1157–1167 (2005).PubMedCrossRefGoogle Scholar
  24. 24.
    24. B. B. Aggarwal, A. Kumar, and A. C. Bharti, Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res 23(1A), 363–398 (2003).PubMedGoogle Scholar
  25. 25.
    25. J. F. Santibanez, M. Quintanilla, and J. Martinez, Genistein and curcumin block TGF-beta 1-induced u-PA expression and migratory and invasive phenotype in mouse epidermal keratinocytes. Nutr Cancer 37(1), 49–54 (2000).PubMedCrossRefGoogle Scholar
  26. 26.
    26. P. C. Smith, J. F. Santibanez, J. P. Morales, and J. Martinez, Epidermal growth factor stimulates urokinase-type plasminogen activator expression in human gingival fibroblasts. Possible modulation by genistein and curcumin. J Periodontal Res 39(6), 380–387 (2004).PubMedCrossRefGoogle Scholar
  27. 27.
    27. M. Parra, F. Lluis, F. Miralles, C. Caelles, and P. Munox-Canoves, The cJun N-terminal kinase (JNK) signaling pathway mediates induction of urokinase-type plasminogen activator (uPA) by the alkylating agent MNNG. Blood 96(4), 1415–1424 (2000).PubMedGoogle Scholar
  28. 28.
    28. T. Collins, M. A. Read, A. S. Neish, M. Z. Whitley, D. Thanos, and T. Maniatis, Transcriptional regulation of endothelial cell adhesion molecules: NF-κ B and cytokine-inducible enhancers. FASEB J 9(10), 899–909 (1995).PubMedGoogle Scholar
  29. 29.
    29. W. G. Stetler-Stevenson, Matrix metalloproteinases in angiogenesis: A moving target for therapeutic intervention. J Clin Invest 103(9), 1237–1241 (1999).PubMedGoogle Scholar
  30. 30.
    30. A. Kumar, S. Dhawan, N. J. Hardegen, and B. B. Aggarwal, Curcumin inhibition of tumor necrosis factor (TNF)-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-κ B activation. Biochem Pharamcol 55, 775–783 (1998).CrossRefGoogle Scholar
  31. 31.
    31. B. Gupta and B. Ghosh, Curcuma longa inhibits TNF-alpha induced expression of adhesion molecules on human umbilical vein endothelial cells. Int J Immunopharmacol. 21, 745–757 (1999).PubMedCrossRefGoogle Scholar
  32. 32.
    32. Aggarwal, D. Thaloor, A. K. Singh, G. S. Sidhu, P. V. Prasad, H. K. Kleinman, R. K. Maheshwari, Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin. Cell growth Differ 9(4), 305–312 (1998).Google Scholar
  33. 33.
    33. S. Aggarwal, H. Ichikawa, Y. Takada, S. K. Sandur, S. Shishodia, and B. B. Aggarwal, Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IκBα Kinase and Akt activation. Mol Pharmacol 69(1), 195–206 (2006).PubMedGoogle Scholar
  34. 34.
    34. D. R. Siwak, S. Shishodia, B. B. Aggarwal, and R. Kurzrock, Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IκB kinase and nuclear factor κB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer 104(4), 879–890 (2005).PubMedCrossRefGoogle Scholar
  35. 35.
    35. J. A. Bush, K.-J. Cheung, Jr., and G. Li, Curcumin induces apoptosis in human melanoma cells through a Fas receptor/easpase 8 pathway independent of p53. Exp Cell Res 271, 305–314 (2001).PubMedCrossRefGoogle Scholar
  36. 36.
    36. P. Dhawan and A. Richmond, A novel NF-κB-inducing kinase-MAPK kinase signaling pathway up-regulates NF-κB activity in melanoma cells. J Biol Chem 277(10), 7920–7928 (2002).PubMedCrossRefGoogle Scholar
  37. 37.
    37. L. V. Madrid, C. Y. Wang, D. C. Guttridge, A. J. Schottelius, A. S. Baldwin, Jr., and M. W. Mayo, Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF–κB. Mol Cell Biol 20, 1626–1638 (2000).PubMedCrossRefGoogle Scholar
  38. 38.
    38. M. Fujita, D. A. Norris, H. Yagi, et al., Overexpression of mutant ras in human melanoma increases invasiveness, proliferation, and anchorage-independent growth in vitro and induces tumour formation and cachexia in vivo. Melanoma Res 9, 279–291 (1999).PubMedCrossRefGoogle Scholar
  39. 39.
    39. J. M. Stahl, M. Cheung, A. Sharma, N. R. Trivedi, S. Shanmugam, and G. P. Robertson, Loss of PTEN promotes tumor development in malignant melanoma. Cancer Res 63, 2881–2890 (2003).PubMedGoogle Scholar
  40. 40.
    40. A. Jetzt, J. A. Howe, M. T. Horn, E. Maxwell, Z. Yin, D. Johnson, C. C. Kumar, Adeno et al., Adenoviral-mediated expression of a kinase-dead mutant of Akt induces apoptosis selectively in tumor cells and suppresses tumor growth in mice. Cancer Res 63, 6697–6706 (2003).PubMedGoogle Scholar
  41. 41.
    41. E. Hoffmann, O. Dittrich-Breiholtz, O. Holtmann, and M. Kracht, Multiple control of interleukin-8 gene expression. J Leuk Biol 72, 847–855 (2002).Google Scholar
  42. 42.
    42. X. Le, Q. Shi, B. Wang, et al., Molecular regulation of constitutive expression of interleukin-8 in human pancreatic adenocarcinoma. J Interferon Cytokine Res 20, 935–946 (2000).PubMedCrossRefGoogle Scholar
  43. 43.
    43. L. I. Lin, Y. F. Ke, Y. C. Ko, and J. K. Lin, Curcumin inhibits SK-Hep-1 hepatocellular carcinoma cell Invasion in vitro and suppresses matrix metalloproteinase-9 secretion Oncology. 55, 349–353 (1998).PubMedCrossRefGoogle Scholar
  44. 44.
    44. P. L. Fox, PG. Sa, S. F. Dobrowolski, and D. W. Stacey, The regulation of endothelial cell motility by p21 ras. Oncogene 9(12), 3519–3526 (1994).PubMedGoogle Scholar
  45. 45.
    45. E. Y. Shin, S. Y. Kim, E. G. Kim, C-Jun N-terminal kinase is involved in motility of endothelial cell. Exp Mol Med 33(4), 276–83 (2001).PubMedGoogle Scholar
  46. 46.
    46. A. C. Bharti, N. Donato, S. Singh, and B. B. Aggarwal, Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-κ B and IκBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 101(3), 1053–1062 (2002).PubMedCrossRefGoogle Scholar
  47. 47.
    47. A. Mukhopadhyay, S. Banerjee, L. J. Stafford, C. Xia, M. Liu, B. B. Aggarwal. Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclic D1 expression and CDK4-medicated retinoblastoma protein phosphorylation. Oncogene 21(57), 8852–8861 (2002.)PubMedCrossRefGoogle Scholar
  48. 48.
    48. Y. Sun, M. P. Wilson, and P. W. Majerus, Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9 signalosome by binding to CSN1. J Biol Chem 277(48), 45759–4564 (2002).PubMedCrossRefGoogle Scholar

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