Nobiletin, a citrus polymethoxyflavonoid, suppresses multiple angiogenesis-related endothelial cell functions and angiogenesis in vivo

Cancer Science

Volumn 101, Issue 11, 2010, Pages 2462-2469

  Kunimasa, Kazuhiro ^a,b   Ikekita, Masahiko ^a   Sato, Mayumi ^c   Ohta, Toshiro ^d   Yamori, Yukio ^b   Ikeda, Megumi ^e   Kuranuki, Sachi ^e   Oikawa, Tsutomu ^e  

^a TOKYO UNIVERSITY OF SCIENCE   (Japan)

^b MUKOGAWA WOMEN'S UNIVERSITY   (Japan)

^c TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE   (Japan)

^d UNIVERSITY OF SHIZUOKA   (Japan)

^e KANAGAWA UNIVERSITY OF HUMAN SERVICES   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ACIDIC FIBROBLAST GROWTH FACTOR; BASIC FIBROBLAST GROWTH FACTOR; CASPASE; ENDOTHELIAL CELL GROWTH FACTOR; GELATIN; GELATINASE A; MATRIGEL; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NOBILETIN; PLASMINOGEN ACTIVATOR; PROTEIN C JUN; STAT3 PROTEIN; STRESS ACTIVATED PROTEIN KINASE; UROKINASE; VASCULOTROPIN;

ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; ARTICLE; CELL DIFFERENTIATION; CELL FUNCTION; CELL MIGRATION; CELL PROLIFERATION; CELL STIMULATION; CHICK EMBRYO; CHORIOALLANTOIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFECT; EMBRYO; ENDOTHELIUM CELL; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME SYNTHESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; NORTHERN BLOTTING; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; UMBILICAL VEIN; ZYMOGRAPHY;

ANIMALS; ANTIOXIDANTS; BLOTTING, NORTHERN; BLOTTING, WESTERN; CELL LINE; CELL MOVEMENT; CELL PROLIFERATION; CHICK EMBRYO; CHORIOALLANTOIC MEMBRANE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOTHELIAL CELLS; ENZYME PRECURSORS; FIBROBLAST GROWTH FACTOR 2; FLAVONES; GENE EXPRESSION; HUMANS; MATRIX METALLOPROTEINASE 2; NEOVASCULARIZATION, PATHOLOGIC; NEOVASCULARIZATION, PHYSIOLOGIC; PLASMINOGEN ACTIVATORS; SIGNAL TRANSDUCTION; UROKINASE-TYPE PLASMINOGEN ACTIVATOR; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 77958611254     PISSN: 13479032     EISSN: 13497006     Source Type: Journal    
DOI: 10.1111/j.1349-7006.2010.01668.x     Document Type: Article

References (61)

1. Folkman J. Clinical applications of research on angiogenesis. N Engl J Med 1995; 333: 1757-63.
2. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407: 249-57.
3. Sato Y. Molecular diagnosis of tumor angiogenesis and anti-angiogenic cancer therapy. Int J Clin Oncol 2003; 8: 200-6.
4. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996; 86: 353-64.
5. Munoz-Chapuli R, Quesada AR, Angel Medina M. Angiogenesis and signal transduction in endothelial cells. Cell Mol Life Sci 2004; 61: 2224-43.
6. Asahara T, Murohara T, Sullivan A et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-7.
7. Oikawa T. Strategies to find novel angiogenesis inhibitors as potential therapeutic agents for cancer. Curr Med Chem 1995; 1: 406-17.
8. Oikawa T. Control of angiogenesis by microbial products. In: Fan T-PD, Kohn EC, eds. The New Angiotherapy. Totowa: Humana Press, 2001; 329-55.
9. Nogata Y, Sakamoto K, Shiratsuchi H, Ishii T, Yano M, Ohta H. Flavonoid composition of fruit tissues of citrus species. Biosci Biotechnol Biochem 2006; 70: 178-92.
10. Murakami A, Nakamura Y, Torikai K et al. Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res 2000; 60: 5059-66.
11. Kohno H, Yoshitani S, Tsukio Y et al. Dietary administration of citrus nobiletin inhibits azoxymethane-induced colonic aberrant crypt foci in rats. Life Sci 2001; 69: 901-13.
12. Suzuki R, Kohno H, Murakami A et al. Citrus nobiletin inhibits azoxymethane-induced large bowel carcinogenesis in rats. Biofactors 2004; 22: 111-4.
13. Minagawa A, Otani Y, Kubota T et al. The citrus flavonoid, nobiletin, inhibits peritoneal dissemination of human gastric carcinoma in SCID mice. Jpn J Cancer Res 2001; 92: 1322-8.
14. Kunimasa K, Kuranuki S, Matsuura N et al. Identification of nobiletin, a polymethoxyflavonoid, as an enhancer of adiponectin secretion. Bioorg Med Chem Lett 2009; 19: 2062-4.
15. Saito T, Abe D, Sekiya K. Nobiletin enhances differentiation and lipolysis of 3T3-L1 adipocytes. Biochem Biophys Res Commun 2007; 357: 371-6.
16. Ishiwa J, Sato T, Mimaki Y, Sashida Y, Yano M, Ito A. A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metalloproteinase 9/gelatinase B in rabbit synovial fibroblasts. J Rheumatol 2000; 27: 20-5.
17. Yajima Y, Sato M, Sumida M, Kawashima S. Mechanism of adult primitive mesenchymal ST-13 preadipocyte differentiation. Endocrinology 2003; 144: 2559-65.
18. Ashino-Fuse H, Takano Y, Oikawa T, Shimamura M, Iwaguchi T. Medroxyprogesterone acetate, an anti-cancer and anti-angiogenic steroid, inhibits the plasminogen activator in bovine endothelial cells. Int J Cancer 1989; 44: 859-64.
19. Aoki K, Watanabe K, Sato M, Ikekita M, Hakamatsuka T, Oikawa T. Effects of rhizoxin, a microbial angiogenesis inhibitor, on angiogenic endothelial cell functions. Eur J Pharmacol 2003; 459: 131-8.
20. Kunimasa K, Kobayashi T, Kaji K, Ohta T. Antiangiogenic effects of indole-3-carbinol and 3, 3'-diindolylmethane are associated with their differential regulation of ERK1/2 and Akt in tube-forming HUVEC. J Nutr 2010; 140: 1-6.
21. Kunimasa K, Ahn MR, Kobayashi T et al. Brazilian propolis suppresses angiogenesis by inducing apoptosis in tube-forming endothelial cells through inactivation of survival signal ERK1/2. Evid Based Complement Alternat Med 2009; doi: 10.1093/ecam/nep024 [Epub ahead of print].
22. Oikawa T, Hirotani K, Nakamura O, Shudo K, Hiragun A, Iwaguchi T. A highly potent antiangiogenic activity of retinoids. Cancer Lett 1989; 48: 157-62.
23. Jain RK. Barriers to drug delivery in solid tumors. Sci Am 1994; 271: 58-65.
24. Morley KL, Ferguson PJ, Koropatnick J. Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells. Cancer Lett 2007; 251: 168-78.
25. Luo G, Guan X, Zhou L. Apoptotic effect of citrus fruit extract nobiletin on lung cancer cell line A549 in vitro and in vivo. Cancer Biol Ther 2008; 7: 966-73.
26. Tang MX, Ogawa K, Asamoto M et al. Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate (TRAP) and human prostate carcinoma cells. Cancer Sci 2007; 98: 471-7.
27. Yoshimizu N, Otani Y, Saikawa Y et al. Anti-tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation. Aliment Pharmacol Ther 2004; 20(Suppl 1): 95-101.
28. Wilhelm SM, Carter C, Tang L et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004; 64: 7099-109.
29. Mavria G, Vercoulen Y, Yeo M et al. ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis. Cancer Cell 2006; 9: 33-44.
30. Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S. Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res 1998; 58: 1048-51.
31. Brooks PC, Silletti S, Von Schalscha TL, Friedlander M, Cheresh DA. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 1998; 92: 391-400.
32. Oikawa T, Ito H, Ashino H et al. Radicicol, a microbial cell differentiation modulator, inhibits in vivo angiogenesis. Eur J Pharmacol 1993; 241: 221-7.
33. Xin X, Yang S, Kowalski J, Gerritsen ME. Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 1999; 274: 9116-21.
34. Cross MJ, Dixelius J, Matsumoto T, Claesson-Welsh L. VEGF-receptor signal transduction. Trends Biochem Sci 2003; 28: 488-94.
35. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev 2005; 16: 139-49.
36. Yang X, Qiao D, Meyer K, Friedl A. Signal transducers and activators of transcription mediate fibroblast growth factor-induced vascular endothelial morphogenesis. Cancer Res 2009; 69: 1668-77.
37. Bartoli M, Gu X, Tsai NT et al. Vascular endothelial growth factor activates STAT proteins in aortic endothelial cells. J Biol Chem 2000; 275: 33189-92.
38. Merchant JL, Du M, Todisco A. Sp1 phosphorylation by Erk 2 stimulates DNA binding. Biochem Biophys Res Commun 1999; 254: 454-61.
39. Eyries M, Agrapart M, Alonso A, Soubrier F. Phorbol ester induction of angiotensin-converting enzyme transcription is mediated by Egr-1 and AP-1 in human endothelial cells via ERK1/2 pathway. Circ Res 2002; 91: 899-906.
40. D'Orazio D, Besser D, Marksitzer R et al. Cooperation of two PEA3/AP1 sites in uPA gene induction by TPA and FGF-2. Gene 1997; 201: 179-87.
41. Qin H, Sun Y, Benveniste EN. The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J Biol Chem 1999; 274: 29130-7.
42. Pan M-R, Hung W-C. Nonsteroidal anti-inflammatory drugs inhibit matrix metalloproteinase-2 via suppression of the ERK/Sp1-mediated transcription. J Biol Chem 2002; 277: 32775-80.
43. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell 2000; 103: 239-52.
44. Sato T, Koike L, Miyata Y et al. Inhibition of activator protein-1 binding activity and phosphatidylinositol 3-kinase pathway by nobiletin, a polymethoxy flavonoid, results in augmentation of tissue inhibitor of metalloproteinases-1 production and suppression of production of matrix metalloproteinases-1 and -9 in human fibrosarcoma HT-1080 cells. Cancer Res 2002; 62: 1025-9.
45. Miyata Y, Sato T, Imada K, Dobashi A, Yano M, Ito A. A citrus polymethoxyflavonoid, nobiletin, is a novel MEK inhibitor that exhibits antitumor metastasis in human fibrosarcoma HT-1080 cells. Biochem Biophys Res Commun 2008; 366: 168-73.
46. Hirata Y, Masuda Y, Kakutani H et al. Sp1 is an essential transcription factor for LPS-induced tissue factor expression in THP-1 monocytic cells, and nobiletin represses the expression through inhibition of NF-kappaB, AP-1, and Sp1 activation. Biochem Pharmacol 2008; 75: 1504-14.
47. Deo DD, Axelrad TW, Robert EG, Marcheselli V, Bazan NG, Hunt JD. Phosphorylation of STAT-3 in response to basic fibroblast growth factor occurs through a mechanism involving platelet-activating factor, JAK-2, and Src in human umbilical vein endothelial cells. Evidence for a dual kinase mechanism. J Biol Chem 2002; 277: 21237-45.
48. Yahata Y, Shirakata Y, Tokumaru S et al. Nuclear translocation of phosphorylated STAT3 is essential for vascular endothelial growth factor-induced human dermal microvascular endothelial cell migration and tube formation. J Biol Chem 2003; 278: 40026-31.
49. Pepper MS, Vassalli JD, Montesano R, Orci L. Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells. J Cell Biol 1987; 105: 2535-41.
50. Schnaper HW, Barnathan ES, Mazar A et al. Plasminogen activators augment endothelial cell organization in vitro by two distinct pathways. J Cell Physiol 1995; 165: 107-18.
51. Odekon LE, Sato Y, Rifkin DB. Urokinase-type plasminogen activator mediates basic fibroblast growth factor-induced bovine endothelial cell migration independent of its proteolytic activity. J Cell Physiol 1992; 150: 258-63.
52. Oikawa T, Hirotani K, Ogasawara H et al. Inhibition of angiogenesis by vitamin D3 analogues. Eur J Pharmacol 1990; 178: 247-50.
53. Oikawa T, Yoshida Y, Shimamura M, Ashino-Fuse H, Iwaguchi T, Tominaga T. Antitumor effect of 22-oxa-1 alpha, 25-dihydroxyvitamin D3, a potent angiogenesis inhibitor, on rat mammary tumors induced by 7, 12-dimethylbenz[a]anthracene. Anticancer Drugs 1991; 2: 475-80.
54. Oikawa T, Okayasu I, Ashino H, Morita I, Murota S, Shudo K. Three novel synthetic retinoids, Re 80, Am 580 and Am 80, all exhibit anti-angiogenic activity in vivo. Eur J Pharmacol 1993; 249: 113-6.
55. Oikawa T, Murakami K, Sano M, Shibata J, Wierzba K, Yamada Y. A potential use of a synthetic retinoid TAC-101 as an orally active agent that blocks angiogenesis in liver metastases of human stomach cancer cells. Jpn J Cancer Res 2001; 92: 1225-34.
56. Oikawa T, Onozawa C, Kuranuki S et al. Dipalmitoylation of radicicol results in improved efficacy against tumor growth and angiogenesis in vivo. Cancer Sci 2007; 98: 219-25.
57. Oikawa T, Sasaki T, Nakamura M et al. The proteasome is involved in angiogenesis. Biochem Biophys Res Commun 1998; 246: 243-8.
58. Oikawa T, Sasaki M, Inose M et al. Effects of cytogenin, a novel microbial product, on embryonic and tumor cell-induced angiogenic responses in vivo. Anticancer Res 1997; 17: 1881-6.
59. Lin N, Sato T, Takayama Y et al. Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages. Biochem Pharmacol 2003; 65: 2065-71.
60. Murakami A, Nakamura Y, Ohto Y et al. Suppressive effects of citrus fruits on free radical generation and nobiletin, an anti-inflammatory polymethoxyflavonoid. Biofactors 2000; 12: 187-92.
61. Ribatti D, Vacca A, Roncali L, Dammacco F. The chick embryo chorioallantoic membrane as a model for in vivo research on anti-angiogenesis. Curr Pharm Biotechnol 2000; 1: 73-82.