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http://dx.doi.org/10.15616/BSL.2014.20.4.209

Novel Anti-Angiogenic Activity in Rubus coreanus Miquel Water Extract Suppresses VEGF-Induced Angiogenesis  

Kim, Eok-Cheon (Division of Biological Science and Technology, Yonsei-Fraunhofer Medical Device Lab., College of Science and Technology, Yonsei University)
Kim, Hye Jin (Division of Biological Science and Technology, Yonsei-Fraunhofer Medical Device Lab., College of Science and Technology, Yonsei University)
Kim, Tack-Joong (Division of Biological Science and Technology, Yonsei-Fraunhofer Medical Device Lab., College of Science and Technology, Yonsei University)
Publication Information
Biomedical Science Letters / v.20, no.4, 2014 , pp. 209-220 More about this Journal
Abstract
Vascular endothelial growth factor (VEGF) is a key factor involved in the induction of angiogenesis and has become an attractive target for anti-angiogenesis therapies. The purpose of this study was to elucidate the anti-angiogenic activity of Rubus coreanus Miquel water extract (RCME). Rubus coreanus Miquel has long been employed as a traditional medicine, and recent studies have demonstrated that it has measureable biological activities. Thus, we investigated for the first time the effect of RCME on angiogenesis and its underlying signaling pathways. The effects of RCME were tested on in vitro models of angiogenesis, namely, proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells as well as an ex vivo model of vessel sprouting from the rat aorta in response to VEGF. We observed that VEGF-induced angiogenesis was strongly suppressed by RCME treatment compared to that of the control group. Moreover, we found that RCME inhibited VEGF-induced activation of matrix metalloproteinases and phosphorylation of extracellular signal-regulated kinase and p38, and also effectively inhibited phosphorylation of VEGF receptor 2. These results indicated that RCME inhibits angiogenesis by suppressing phosphorylation of the VEGF receptor and may be useful for the treatment of angiogenesis-dependent diseases such as cancer and diabetic retinopathy.
Keywords
Angiogenesis; Rubus coreanus Miquel; VEGF receptor phosphorylation;
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1 Lu N, Gao Y, Ling Y, Chen Y, Yang Y, Gu HY, Qi Q, Liu W, Wang XT, You QD, Guo QL. Wogonin suppresses tumor growth in vivo and VEGF-induced angiogenesis through inhibiting tyrosine phosphorylation of VEGFR2. Life Sci. 2008. 82: 956-963.   DOI   ScienceOn
2 Matsunaga N, Shimazawa M, Otsubo K, Hara H. Phosphatidylinositol inhibits vascular endothelial growth factor-A--induced migration of human umbilical vein endothelial cells. J Pharmacol Sci. 2008. 106: 128-135.   DOI
3 Mustonen T, Alitalo K. Endothelial receptor tyrosine kinases involved in angiogenesis. J Cell Biol. 1995. 129: 895-898.   DOI   ScienceOn
4 Nam JH, Jung HJ, Choi J, Lee KT, Park HJ. The anti-gastropathic and anti-rheumatic effect of niga-ichigoside F1 and 23-hydroxytormentic acid isolated from the unripe fruits of Rubus coreanus in a rat model. Biol Pharm Bull. 2006. 29: 967-970.   DOI   ScienceOn
5 Oppenheim J, Fujiwara H. The role of cytokines in cancer. Cytokine Growth Factor Rev. 1996. 7: 279-288.   DOI
6 Rao CV, Rivenson A, Simi B, Reddy BS. Chemoprevention of colon cancer by dietary curcumin. Ann N Y Acad Sci. 1995. 768: 201-204.   DOI
7 Risau W. Differentiation of endothelium. FASEB J. 1995. 9: 926-933.   DOI
8 Rousseau S, Houle F, Landry J, Huot J. p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells. Oncogene 1997. 15: 2169-2177.   DOI
9 Sage EH. Pieces of eight: bioactive fragments of extracellular proteins as regulators of angiogenesis. Trends Cell Biol. 1997. 7: 182-186.   DOI
10 Shaheen RM, Davis DW, Liu W, Zebrowski BK, Wilson MR, Bucana CD, McConkey DJ, McMahon G, Ellis LM. Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and incuces tumor and endothelial cell apoptosis. Cancer Res. 1999. 59: 5412-5416.
11 Stoclet JC, Chataigneau T, Ndiaya M, Oak MH, El Bedoui J, Chataiqneau M, Schini-Kerth VB. Vascular protection by dietary polyphenols. Eur J Pharmacol. 2004. 500: 299-313.   DOI
12 Takahashi T, Ueno H, Shibuya M. VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells. Oncogene. 1999. 18: 2221-2230.   DOI   ScienceOn
13 Van Moorselaar RJ, Voest EE. Angiogenesis in prostate cancer: its role in disease progression and possible therapeutic approaches. Mol Cell Endocrinol. 2002. 197: 239-250.   DOI
14 Wen W, Lu J, Zhang K, Chen S. Grape seed extract inhibits angiogenesis via suppression of the vascular endothelial growth factor receptor signaling pathway. Cancer Prev Res (Phila). 2008. 1: 554-561.   DOI
15 Yance DR, Sagar SM. Targeting angiogenesis with integrative cancer therapies. Integr Cancer Ther. 2006. 5: 9-29.   DOI
16 Yoshiji H, Kuriyama S, Hicklin DJ, Huber J, Yoshii J, Miyamoto Y, Kawata M, Ikenaka Y, Nakatani T, Tsujinoue H, Fukui H. KDR/Flk-1 is a major regulator of vascular endothelial growth factor-induced tumor development and angiogenesis in murine hepatocellular carcinoma cells. Hepatology. 1999. 30: 1179-1186.   DOI
17 Agarwal R, Agarwal C, Ichikawa H, Singh RP, Aggarwal BB. Anticancer potential of silymarin: from bench to bed side. Anticancer Res. 2006. 26: 4457-4498.
18 Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA, Kozlowski JM, McEwan RN. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 1987. 47: 3239-3245.
19 Balbay MD, Pettaway CA, Kuniyasu H, Inoue K, Ramirez E, Li E, Fidler IJ, Dinney CP. Highly metastatic human prostate cancer growing within the prostate of athymic mice overexpresses vascular endothelial growth factor. Clin Cancer Res. 1999. 5: 783-789.
20 Bussolino F, Mantovani A, Persico G. Molecular mechanisms of blood vessel formation. Trends Biochem Sci. 1997. 22: 251-256.   DOI
21 Cardenas C, Quesada AR, Medina MA. Anti-angiogenic and anti-inflammatory properties of kahweol, a coffee diterpene. PLoS One. 2011. 6: e23407.   DOI
22 Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003. 9: 653-660.   DOI   ScienceOn
23 Chrzanowska-Wodnicka M, Kraus AE, Gale D, White GC, Vansluys J. Defective angiogenesis, endothelial migration, proliferation, and MAPK signaling in Rap1b-deficient mice. Blood. 2008. 111: 2647-2656.   DOI   ScienceOn
24 Droller MJ. Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer. J Urol. 1998. 160: 1932.   DOI   ScienceOn
25 Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003. 9: 669-676.   DOI   ScienceOn
26 Dulak J, Jozkowicz A. Regulation of vascular endothelial growth factor synthesis by nitric oxide: facts and controversies. Antioxid Redox Signal. 2003. 5: 123-132.   DOI
27 Dulak J. Nutraceuticals as anti-angiogenic agents: hopes and reality. J Physiol Pharmacol. 2005. 56: (suppl.) 51-67.
28 Erdemoglu N, Kupeli E, Yesilada E. Anti-inflammatory and antinociceptive activity assessment of plants used as remedy in Turkish folk medicine. J Ethnopharmacol. 2003. 89: 123-129.   DOI
29 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995. 1: 27-31.   DOI   ScienceOn
30 Folkman J. Angiogenesis. Annu Rev Med. 2006. 57: 1-18.   DOI   ScienceOn
31 Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996. 86: 354-364.
32 Hanemaaijer R, Koolwijk P, Le Clercq L, De Vree WJ, Van Hinsbergh VW. Regulation of matrix metalloproteinase expression in human vein and microvascular endothelial cells. Effects of tumour necrosis factor alpha, interleukin 1 and phorbol ester. Biochem J. 1993. 296: 803-809.   DOI
33 Huang C, Jacobson K, Schaller MD. MAP kinases and cell migration. J Cell Sci. 2004. 117: 4619-4628.   DOI
34 Kabbinavar FF, Hambleton J, Mass RD, Hurwiz HI, Bergsland E, Sarkar S. Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol. 2005. 23: 3706-3712.   DOI   ScienceOn
35 Kim EH, Na HK, Surh YJ. Upregulation of VEGF by 15-deoxy-Delta12,14-prostaglandin J2 via heme oxygenase-1 and ERK1/2 signaling in MCF-7 cells. Ann N Y Acad Sci. 2006. 1090: 375-384.   DOI
36 Kruger EA, Duray PH, Tsokos MG, Venzon DJ, Libutti SK, Dixon SC, Rudek MA, Pluda J, Allegra C, Figg WD. Endostatin inhibits microvessel formation in the ex vivo rat aortic ring angiogenesis assay. Biochem Biophys Res Commun. 2000. 268: 183-191.   DOI
37 Kim Y, Kim J, Lee SM, Lee HA, Park S, Kim Y, Kim JH. Chemopreventive effects of Rubus coreanus Miquel on prostate cancer. Biosci Biotechnol Biochem. 2012. 76: 737-744.   DOI   ScienceOn
38 Kitamura M, Toi M, Arai K, Iwasaki Y, Suzuki H, Matsuo K. Concerntarations of vascular endothelial growth factor in the sera of gastric cancer patients. Oncol Rep. 1998. 5: 1419-1424.
39 Ko SH, Choi SW, Ye SK, Yoo SH, Kim HS, Chung MH. Comparison of anti-oxidant activities of seventy herbs that have been used in Korean traditional medicine. Nutr Res Pract. 2008. 2: 143-151.   DOI
40 Kurebayashi J, Otsuki T, Kunisue H, Mikami Y, Tanaka K, Yamamoto S, Sonoo H. Expression of vascular endothelial growth factor (VEGF) family members in breast cancer. Jpn J Cancer Res. 1999. 90: 977-981.   DOI
41 Leber TM, Balkwill FR. Zymography: a single-step staining method for quantitation of proteolytic activity on substrate gels. Anal Biochem. 1997. 249: 24-28.   DOI
42 Lee JE, Park EK, Lee JE, Auh JH, Choi HK, Lee JH, Cho SM, Kim JH, Kim YR. Effects of a Rubus coreanus Miquel supplement on plasma antioxidant capacity in healthy Korean men. Nutr Res Pract. 2011. 5: 429-434.   DOI   ScienceOn
43 Lee OH, Kim YM, Lee YM, Moon EJ, Lee DJ, Kim JH, Kim KW, Kwon YG. Sphingosine 1-phosphate induces angiogenesis: its angiogenic action and signaling mechanism in human umbilical vein endothelial cells. Biochem Biophys Res Commun. 1999. 264: 743-750.   DOI   ScienceOn
44 Lee SY, Chung SM. Neovastat (AE-941) inhibits the airway inflammation via VEGF and HIF-2 alpha suppression. Vascul Pharmacol. 2007. 47: 313-318.   DOI   ScienceOn
45 Lin JK, Chen YC, Huang YT, Lin-Shiau SY. Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin. J Cell Biochem. 1997. 28/29: 39-48.