期刊论文详细信息
BMC Complementary and Alternative Medicine
Ethanol extract of Gleditsia sinensis thorn suppresses angiogenesis in vitro and in vivo
No Soo Kim1  Ok-Sun Bang1  Dal-Seok Oh1  Jinhee Kim1  Jun Lee1  Se-Mi Oh1  Jong-Shik Park1  Jin-Mu Yi1 
[1] KM-Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea
关键词: Medicinal herb;    Gene expression;    Anticancer;    Antiangiogenesis;    Gleditsia sinensis thorn;   
Others  :  1231423
DOI  :  10.1186/1472-6882-12-243
 received in 2012-07-30, accepted in 2012-11-29,  发布年份 2012
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【 摘 要 】

Background

Gleditsia sinensis thorns have been widely used in traditional Korean medicine for the treatment of several diseases, including obesity, thrombosis, and tumor-related diseases. The aim of the study is to determine the antiangiogenic effect of Gleditsia sinensis thorns in vitro and in vivo in a bid to evaluate its potential as an anticancer drug.

Methods

Ethanol extract of Gleditsia sinensis thorns (EEGS) were prepared and used for in vitro and in vivo assays. In vitro antiangiogenic effect of EEGS was determined in HUVEC primary cells by cell migration and tube formation assays. In vivo antiangiogenic effect of EEGS was determined by measuring vessel formation and vascular endothelial cells migrating into the implanted matrigels in nude mice. The angiogenesis-related proteins of which expression levels were altered by EEGS were identified by proteomic analysis.

Results

EEGS exerted a dose-dependent antiproliferative effect on HUVEC cells without significant cytotoxicity. Angiogenic properties, such as cell migration and tube formation, were significantly inhibited by EEGS in a dose-dependent manner. New vessel formation was also suppressed by EEGS, as determined by the directed in vivo angiogenesis assays in nude mice. EEGS reduced the expression of proangiogenic proteins, endothelin 1 and matrix metallopeptidase 2, in HUVEC cells.

Conclusions

Our findings suggest that EEGS can inhibit angiogenesis by down-regulating proangiogenic proteins, and therefore it should be considered as a potential anticancer drug targeting tumor-derived angiogenesis.

【 授权许可】

   
2012 Yi et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Matsunaga N, Chikaraishi Y, Shimazawa M, Yokota S, Hara H: Vaccinium myrtillus (bilberry) extracts reduce angiogenesis In vitro and In vivo. Evid Based Complement Alternat Med 2010, 7:47-56.
  • [2]Tandle A, Blazer DG 3rd, Libutti SK: Antiangiogenic gene therapy of cancer: recent developments. J Transl Med 2004, 2:22. BioMed Central Full Text
  • [3]Papetti M, Herman IM: Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol 2002, 282:C947-C970.
  • [4]Tosetti F, Ferrari N, De Flora S, Albini A: Angioprevention: angiogenesis is a common and key target for cancer chemopreventive agents. FASEB J 2002, 16:2-14.
  • [5]Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med 1971, 285:1182-1186.
  • [6]Boehm T, Folkman J, Browder T, O'Reilly MS: Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997, 390:404-407.
  • [7]Ferrara N, Gerber HP, LeCouter J: The biology of VEGF and its receptors. Nat Med 2003, 9:669-676.
  • [8]Dai Y, Chan YP, Chu LM, Bu PP: Antiallergic and anti-inflammatory properties of the ethanolic extract from gleditsia sinensis. Biol Pharm Bull 2002, 25:1179-1182.
  • [9]Lai P, Du JR, Zhang MX, Kuang X, Li YJ, Chen YS, He Y: Aqueous extract of gleditsia sinensis Lam. Fruits improves serum and liver lipid profiles and attenuates atherosclerosis in rabbits fed a high-fat diet. J Ethnopharmacol 2011, 137:1061-1066.
  • [10]Lee SJ, Park K, Ha SD, Kim WJ, Moon SK: Gleditsia sinensis thorn extract inhibits human colon cancer cells: the role of ERK1/2, G2/M-phase cell cycle arrest and p53 expression. Phytother Res 2010, 24:1870-1876.
  • [11]Long L, Geng GX, Li QW: Effect of gleditsia sinensis stings on growth inhibition and expression of PCNA and p53 in mice bearing uterine cervical carcinoma (U14). Zhongguo Zhong Yao Za Zhi 2006, 31:150-153.
  • [12]Chui CH, Lau FY, Chan AS, Cheng GY, Wong RS, Lai KB, Kok SH, Yeung TT, Teo IT, Yau MY, et al.: Gleditsia sinensis fruit extract-induced apoptosis involves changes of reactive oxygen species level, mitochondrial membrane depolarization and caspase 3 activation. Int J Mol Med 2005, 15:539-543.
  • [13]Pak KC, Lam KY, Law S, Tang JC: The inhibitory effect of gleditsia sinensis on cyclooxygenase-2 expression in human esophageal squamous cell carcinoma. Int J Mol Med 2009, 23:121-129.
  • [14]Lee SJ, Park SS, Kim WJ, Moon SK: Gleditsia sinensis thorn extract inhibits proliferation and TNF-alpha-induced MMP-9 expression in vascular smooth muscle cells. Am J Chin Med 2012, 40:373-386.
  • [15]Asakage M, Tsuno NH, Kitayama J, Tsuchiya T, Yoneyama S, Yamada J, Okaji Y, Kaisaki S, Osada T, Takahashi K, et al.: Sulforaphane induces inhibition of human umbilical vein endothelial cells proliferation by apoptosis. Angiogenesis 2006, 9:83-91.
  • [16]Salani D, Taraboletti G, Rosano L, Di Castro V, Borsotti P, Giavazzi R, Bagnato A: Endothelin-1 induces an angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Am J Pathol 2000, 157:1703-1711.
  • [17]Cardenas C, Quesada AR, Medina MA: Anti-angiogenic and anti-inflammatory properties of kahweol, a coffee diterpene. PLoS One 2011, 6:e23407.
  • [18]Wong KK: Searching for a magic bullet in NSCLC: the role of epidermal growth factor receptor mutations and tyrosine kinase inhibitors. Lung Cancer 2008, 60(Suppl 2):10-18.
  • [19]Dimitrov DS, Marks JD: Therapeutic antibodies: current state and future trends–is a paradigm change coming soon? Methods Mol Biol 2009, 525:1-27.
  • [20]Baguley BC: Multiple drug resistance mechanisms in cancer. Mol Biotechnol 2010, 46:308-316.
  • [21]Folkman J, Merler E, Abernathy C, Williams G: Isolation of a tumor factor responsible for angiogenesis. J Exp Med 1971, 133:275-288.
  • [22]Lord S, Harris AL: Angiogenesis - still a worthwhile target for breast cancer therapy? Breast Cancer Res 2010, 12(Suppl 4):19. BioMed Central Full Text
  • [23]Planchard D: Bevacizumab in non-small-cell lung cancer: a review. Expert Rev Anticancer Ther 2011, 11:1163-1179.
  • [24]Scott LJ: Bevacizumab: in first-line treatment of metastatic breast cancer. Drugs 2007, 67:1793-1799.
  • [25]Kumaran G, Clamp AR, Jayson GC: Angiogenesis as a therapeutic target in cancer. Clin Med 2008, 8:455-458.
  • [26]Pasquier E, Carre M, Pourroy B, Camoin L, Rebai O, Briand C, Braguer D: Antiangiogenic activity of paclitaxel is associated with its cytostatic effect, mediated by the initiation but not completion of a mitochondrial apoptotic signaling pathway. Mol Cancer Ther 2004, 3:1301-1310.
  • [27]Lu D, Xia Y, Tong B, Zhang C, Pan R, Xu H, Yang X, Dai Y: In vitro anti-angiogenesis effects and active constituents of the saponin fraction from gleditsia sinensis. Integr Cancer Ther 2012.
  • [28]Bagnato A, Rosano L: The endothelin axis in cancer. Int J Biochem Cell Biol 2008, 40(8):1443-1451.
  • [29]Miyake JA, Benadiba M, Colquhoun A: Gamma-linolenic acid inhibits both tumour cell cycle progression and angiogenesis in the orthotopic C6 glioma model through changes in VEGF, Flt1, ERK1/2, MMP2, cyclin D1, pRb, p53 and p27 protein expression. Lipids Health Dis 2009, 8:8. BioMed Central Full Text
  • [30]Lu MK, Chen PH, Shih YW, Chang YT, Huang ET, Liu CR, Chen PS: Alpha-chaconine inhibits angiogenesis in vitro by reducing matrix metalloproteinase-2. Biol Pharm Bull 2010, 33:622-630.
  • [31]Zhang Z, Koike K, Jia Z, Nikaido T, Guo D, Zheng J: Four new triterpenoidal saponins acylated with one monoterpenic acid from gleditsia sinensis. J Nat Prod 1999, 62:740-745.
  • [32]Wu J, Li J, Zhu Z, Huang G, Tang Y, Gao X: Protective effects of echinocystic acid isolated from gleditsia sinensis Lam. Against acute myocardial ischemia. Fitoterapia 2010, 81:8-10.
  • [33]Yu S, Park JS, Paredes V, Song MC, Baek NI, Lee SI, Lim JS, Cho NY, Yoon J, Baek K: Screening and isolation of a natural dopamine D1 receptor antagonist using cell-based assays. J Biotechnol 2010, 145:304-309.
  • [34]Zhang Z, Koike K, Jia Z, Nikaido T, Guo D, Zheng J: Triterpenoidal saponins from gleditsia sinensis. Phytochemistry 1999, 52:715-722.
  • [35]Zhang WY, Lee JJ, Kim IS, Kim Y, Myung CS: Stimulation of glucose uptake and improvement of insulin resistance by aromadendrin. Pharmacology 2011, 88:266-274.
  • [36]Zhou L, Li D, Jiang W, Qin Z, Zhao S, Qiu M, Wu J: Two ellagic acid glycosides from gleditsia sinensis Lam. With antifungal activity on magnaporthe grisea. Nat Prod Res 2007, 21:303-309.
  • [37]Zhang Z, Koike K, Jia Z, Nikaido T, Guo D, Zheng J: Gleditsiosides N-Q, new triterpenoid saponins from gleditsia sinensis. J Nat Prod 1999, 62:877-881.
  • [38]Zhong L, Qu G, Li P, Han J, Guo D: Induction of apoptosis and G2/M cell cycle arrest by gleditsioside E from gleditsia sinensis in HL-60 cells. Planta Med 2003, 69:561-563.
  • [39]Gao ZZ, Xia YF, Yao XJ, Dai Y, Wang Q: A new triterpenoid saponin from gleditisia sinensis and structure-activity relationships of inhibitory effects on lipopolysaccharide-induced nitric oxide production. Nat Prod Res 2008, 22:320-332.
  • [40]Zhang Z, Koike K, Jia Z, Nikaido T, Guo D, Zheng J: Triterpenoidal saponins acylated with two monoterpenic acids from gleditsia sinensis. Chem Pharm Bul 1999, 47:388-393.
  • [41]Chong W, Feng XY, Zhen GZ, Dan L, Yue D: Inhibition of mast cell degranulation by saponins from gleditsia sinensis–structure-activity relationships. Nat Prod Commun 2009, 4:777-782.
  • [42]Li WH, Zhang XM, Tian RR, Zheng YT, Zhao WM, Qiu MH: A new anti-HIV lupane acid from Gleditsia sinensis Lam. J Asian Nat Prod Res 2007, 9:551-555.
  • [43]Lim JC, Park JH, Budesinsky M, Kasal A, Han YH, Koo BS, Lee SI, Lee DU: Antimutagenic constituents from the thorns of gleditsia sinensis. Chem Pharm Bul 2005, 53:561-564.
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