Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-Angiogenic Activity of Gecko Aqueous Extracts and its Macromolecular Components in CAM and HUVE-12 Cells

  • Tang, Zhen (Department of Biological Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine) ;
  • Huang, Shu-Qiong (Department of Biological Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine) ;
  • Liu, Jian-Ting (Department of Biological Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine) ;
  • Jiang, Gui-Xiang (Department of Biological Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine) ;
  • Wang, Chun-Mei (Department of Biological Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine)
  • Published : 2015.03.18
Download PDF
⟨ Previous Next ⟩

Abstract

Gecko is a kind of traditional Chinese medicine with remarkable antineoplastic activity. However, undefined mechanisms and ambiguity regarding active ingredients limit new drug development from gecko. This study was conducted to assess anti-angiogenic properties of the aqueous extracts of fresh gecko (AG) or macromolecular components separated from AG (M-AG). An enzyme-linked immunosorbent assay (ELISA) approach was applied to detect the vascular endothelial growth factor (VEGF) secretion of the tumor cells treated with AG or M-AG. The effect of AG or M-AG on vascular endothelial cell proliferation and migratory ability was analyzed by tetrazolium dye colorimetric method, transwell and wound-healing assays. Chick embryo chorioallantoic membrane (CAM) assays were used to ensure the anti-angiogenic activity of M-AG in vivo. The results showed that AG or M-AG inhibited the VEGF secretion of tumor cells, the relative inhibition rates of AG and M-AG being 27.2% and 53.2% respectively at a concentration of $20{\mu}L/mL$. AG and M-AG inhibited the vascular endothelial (VE) cell proliferation with IC50 values of $11.5{\pm}0.5{\mu}L/mL$ and $12.9{\pm}0.4{\mu}L/mL$ respectively. The VE cell migration potential was inhibited significantly (p<0.01) by the AG (${\geq}24{\mu}L/mL$) or M-AG (${\geq}12\mu}L/mL$) treatment. In vivo, neovascularization of CAM treated with M-AG was inhibited significantly (p<0.05) at a concentration of ${\geq}0.4{\mu}L/mL$. This study provided evidence that anti-angiogenesis is one of the anti-tumor mechanisms of AG and M-AG, with the latter as a promising active component.

Keywords

References

  1. Auerbach R, Lewis R, Shinners B, et al (2003). Angiogenesis assays: a critical overview. Clin Chem, 49, 32-40. https://doi.org/10.1373/49.1.32
  2. Brooks PC, Montgomery AM, Cheresh DA (1999). Use of the 10-day-old chick embryomodel for studying angiogenesis. Methods Mol Biol, 129, 257-69.
  3. Chen SL, Burnett J, Sun D, et al (2013). Photoacoustic microscopy: a potential new tool for evaluation of angiogenesis inhibitor. Biomed Opt Express, 4, 2657-66. https://doi.org/10.1364/BOE.4.002657
  4. Folkman J (1972). Anti-angiogenesis: new concept for therapy of solid tumours. Ann Surg, 175, 409-16. https://doi.org/10.1097/00000658-197203000-00014
  5. Folkman J, Klagsbrun M (1987). Angiogenetic factors. Scinece, 235, 442-7. https://doi.org/10.1126/science.2432664
  6. Hou XN, Geng D, Cai A, et al (2008). Comparative research on anticancer activity between fresh and processed gekko subpalmatus. Zhong Yao Cai, 31, 957-9.
  7. Jeong AJ, Chung CN, Kim HJ, et al (2012). Gecko proteins exert anti-tumour effect against cervical cancer cells via PI3-Kinase/Akt pathway. Korean J Physiol Pharmacol, 16, 361-5. https://doi.org/10.4196/kjpp.2012.16.5.361
  8. Jiang G, Wang C, Geng D, et al (2014). Advances on the antitumor material finding from gecko and the mechanism research. Curr Opin Complement Alternat Med, 1, 45-8.
  9. Kang JG, Zhang SZ, Li ZZ, et al (2009). Preparation of fresh Gekko swinhon is gunther anti-neoplasm active component alkaloid liposomes and its quality evaluation. Chinese J New Drugs, 18, 1453-8.
  10. Li YP, Tian FG, Shi PC, et al (2014). 4-Hydroxynonenal promotes growth and angiogenesis of breast cancer cells through HIF-$1{\alpha}$ stabilization. Asian Pac J Cancer Prev, 15, 10151-6.
  11. Limaverde-Sousa G, Sternberg C, Ferreira CG (2014). Antiangiogenesis beyond VEGF inhibition: a journey from antiangiogenic single-target to broad-spectrum agents. Cancer Treat Rev, 40, 548-57. https://doi.org/10.1016/j.ctrv.2013.11.009
  12. Liu F, Wang JG, Wang SY, et al (2008). Antitumour effect and mechanism of Gecko on human esophageal carcinoma cell lines in vitro and xenografted sarcoma 180 in Kunming mice. World J Gastroenterol, 14, 3990-6. https://doi.org/10.3748/wjg.14.3990
  13. Liu S, Sun Y, Louie W (2015). Symptom distress and its association with traditional chinese medicine use in chineseamerican women with cancer. Oncol Nurs Forum, 42, 24-32. https://doi.org/10.1188/15.ONF.24-32
  14. Los M, Roodhart JML, Voest EE (2007). Target practice: lessons from phase III trials with bevacizumab and vatalanib in the treatment of advanced colorectal cancer. Oncologist, 12, 443-50. https://doi.org/10.1634/theoncologist.12-4-443
  15. Lou YL, Guo F, Liu F (2012). MiR-210 activates notch signaling pathway in angiogenesis induced by cerebral ischemia. Mol Cell Biochem, 370, 45-51. https://doi.org/10.1007/s11010-012-1396-6
  16. Mosmann T (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  17. Naqane M (2014). Anti-angiogenic therapy for malignant glioma. Gan To Kagaku Ryoho, 41, 141-7.
  18. Polverini PJ (2002). Angiogenesis in health and disease: Insights into basic mechanisms and therapeutic opportunities. J Dent Educ, 66, 962-75.
  19. Sinclair S (1998). Chinese herbs: a clinical review of astragalus, ligusticum, and schizandrae. Altern Med Rev, 3, 338-44.
  20. Song JY, Wang XL, Wang JG, et al (2011). Inhibitory effects of gecko alcohol extract on human esophageal squamous carcinoma cell line EC-109 proliferation and associated mechanism. Zhong Yao Cai, 34, 1020-3.
  21. Sun Y (2014). The role of Chinese medicine in clinical oncology. Chin J Integr Med, 20, 3-10. https://doi.org/10.1007/s11655-013-1551-2
  22. Wang C, Cao J, Qu J (2010). Recombinant vascular basement membrane derived multifunctional peptide blocks endothelial cell angiogenesis and neovascularization. J Cell Biochem, 111, 453-60. https://doi.org/10.1002/jcb.22735
  23. Wang F, Hu J, Xiong L, et al (2014). Effects of klotho protein on proliferation, migration, adhesion and vascular endothelial growth factor expression of human umbilical vein cells. Zhonghua Yi Xue Za Zhi, 94, 2207-11.
  24. Wang YX, Gu XX, Geng D, et al (2014). Differentiation of bel-7402 human hepatocarcinoma cells induced by aqueous extracts of fresh gecko (AG) and its anti-tumor activity in vivo. J Ethnopharmacol, 155, 1583-8. https://doi.org/10.1016/j.jep.2014.07.050
  25. Wu XL, Wang JG, Li RF, et al (2013). Inhibitory effect of Gecko peptides mixture on growth of human esophageal squamous carcinoma cell line EC109 cells. Chin J Clin Pharmacol, 29, 602-4.
  26. Wu XZ, Xie GR (2008). Induced differentiation of hepatocellular carcinoma by natural products. Afr J Tradit Complement Altern Med, 5, 325-31.
  27. Xin L, Wu XZ, Xie GR (2011). Efffects of gekko sulfated polysaccharide on the proliferation and differentiation in hepatic cancer cell line SMMC-7721. Tianjin Med J, 39, 1123-6.
  28. Yang JX, Wang XM, Zhu W, et al (2007). Anti-tumour effects of dry and fresh gekko swinhonis gunther freeze-dried powders on mouse H22 hepatocellular carcinoma in vivo and in vitro. World Chinese J Digestol, 15, 157-60.
  29. Yang R, Guo JH, Jiang Y (2003). Analysis of application and utilization of anti-tumour drugs and its assistant patent Chinese Drugs. Zhongguo Zhong Xi Yi Jie He Za Zhi, 23, 946-9.
  30. Yarrow JC, Perlman ZE, Westwood NJ (2004). A highthroughput cell migration assay using scratch wound healing, a comparison of image-based readout methods. BMC Biotechnol, 4, 21. https://doi.org/10.1186/1472-6750-4-21
  31. Zeng RX (2012). Analysis of the utilization of antitumour drugs of Chinese patent medicines in our hospital during 2009-