Celastrus Orbiculatus Extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo

Ya-yun Qian; Hua Zhang; Ying Hou; Lin Yuan; Guo-qing Li; Shi-yu Guo; Tadashi Hisamits; Yan-qing Liu

doi:10.1007/s11655-011-0819-7

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Celastrus Orbiculatus Extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo

OriginalPaper | Updated：2021-08-27

- Celastrus Orbiculatus Extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo
- Celastrus Orbiculatus Extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo
- 中国结合医学杂志（英文版） 2012年18卷第10期页码：752-760
- Affiliations：
  
  1. Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University,Jiangsu Province,Yangzhou,China
  2. Department of Image, 97th Hospital of People’s Liberation Army,Jiangsu Province,Xuzhou,China
  3. Department of Physiology, School of Medicine, Showa University,Tokyo,Japan
- Author bio：
- Funds：
  
  Supported by Plans of Colleges and Universities in Jiangsu Province to Postgraduate Research and Innovation (No. CX09B-321Z) and State Administration of Traditional Chinese Medicine of People’s Republic of China (No. 04-05ZP35)
- DOI：10.1007/s11655-011-0819-7
  中图分类号：
- 纸质出版日期：2012，
  
  网络出版日期：2011-7-30，
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Qian, Yy., Zhang, H., Hou, Y. et al. , Celastrus Orbiculatus Extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo, ., Chin. J. Integr. Med. 18, 752–760 (2012). https://doi.org/10.1007/s11655-011-0819-7

Ya-yun Qian, Hua Zhang, Ying Hou, et al. Celastrus Orbiculatus Extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo[J]. Chinese Journal of Integrative Medicine, 2012,18(10):752-760.
Qian, Yy., Zhang, H., Hou, Y. et al. , Celastrus Orbiculatus Extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo, ., Chin. J. Integr. Med. 18, 752–760 (2012). https://doi.org/10.1007/s11655-011-0819-7 DOI：

Ya-yun Qian, Hua Zhang, Ying Hou, et al. Celastrus Orbiculatus Extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo[J]. Chinese Journal of Integrative Medicine, 2012,18(10):752-760. DOI： 10.1007/s11655-011-0819-7.

摘要

Celastrus orbiculatus Thunb. has been used for thousands of years in China as a remedy against cancer and inflammatory diseases. This study aims to investigate whether C. orbiculatus extract (COE) could inhibit angiogenesis

which is the pivotal step in tumor growth

invasiveness

and metastasis. In this study

the extract from the stem of C. orbiculatus was used. Mouse hepatic carcinoma cells (Hepa1-6) were treated with COE in different nontoxic concentrations (10

and 160 μg/mL). The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot

respectively; the active fractions were further tested on C57BL/6 mice and human umbilical vein endothelial cells (HUVEC) for any antiangiogenic effects. COE significantly inhibited proliferation and induced apoptosis in Hepa1-6 cells and inhibited VEGF expression at both mRNA and protein levels. Furthermore

this agent inhibited the formation of the capillary-like structure in primary cultured HUVEC in a dose-dependent manner. In vivo

COE significantly reduced the volume and weight of solid tumors with low adverse effects and decreased tumor angiogenesis. In summary

COE could be used to treat hepatic carcinoma. The mechanisms of the antitumor activity of COE may be due to its effects against tumor angiogenesis by targeting the VEGF protein.

Abstract

which is the pivotal step in tumor growth

invasiveness

and metastasis. In this study

the extract from the stem of C. orbiculatus was used. Mouse hepatic carcinoma cells (Hepa1-6) were treated with COE in different nontoxic concentrations (10

and 160 μg/mL). The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot

this agent inhibited the formation of the capillary-like structure in primary cultured HUVEC in a dose-dependent manner. In vivo

COE significantly reduced the volume and weight of solid tumors with low adverse effects and decreased tumor angiogenesis. In summary

COE could be used to treat hepatic carcinoma. The mechanisms of the antitumor activity of COE may be due to its effects against tumor angiogenesis by targeting the VEGF protein.

关键词

antitumorCelastrus orbiculatus Thunb.angiogenesisvascular endothelial growth factor

Keywords

antitumorCelastrus orbiculatus Thunb.angiogenesisvascular endothelial growth factor

references

Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182–1186.

Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249–257.

Carmeliet P, Baes M. Metabolism and therapeutic angiogenesis. N Engl J Med 2008;358:2511–2512.

Burstein HJ, Schwartz RS. Molecular origins of cancer. N Engl J Med 2008;358:527.

Kerbel RS. Tumor angiogenesis. N Engl J Med 2008;358:2039–2049.

Reinacher-Schick A, Pohl M, Schmiegel W. Drug insight: antiangiogenic therapies for gastrointestinal cancers-focus on monoclonal antibodies. Nat Clin Pract Gastroenterol Hepatol 2008;5:250–267.

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378–390.

Jin HZ, Hwang BY, Kim HS, Lee JH, Kim YH, Lee JJ. Antiinflammatory constituents of Celastrus orbiculatus inhibit the NF-kappaB activation and NO production. J Nat Prod 2002;65:89–91.

Chen S, Gao J, Halicka HD, Huang X, Traganos F, Darzynkiewicz Z. The cytostatic and cytotoxic effects of oridonin (Rubescenin), a diterpenoid from Rabdosia rubescens, on tumor cells of different lineage. Int J Oncol 2005; 26: 579–588.

Ikezoe T, Chen SS, Tong XJ, Heber D, Taguchi H, Koeffler HP. Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells. Int J Oncol 2003;23:1187–1193.

Wang KW. A new fatty acid ester of triterpenoid from Celastrus rosthornianus with anti-tumor activities. Nat Prod Res 2007;21:669–674.

Zhang CL, Wu LJ, Zuo HJ, Tashiro S, Onodera S, Ikejima T. Cytochrome c release from oridonin-treated apoptotic A375-S2 cells is dependent on p53 and extracellular signal-regulated kinase activation. J Pharmacol Sci 2004; 96:155–163.

Zhou GB, Kang H, Wang L, Gao L, Liu P, Xie J, et al. Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21) leukemia in vitro and in vivo. Blood 2007;109:3441–3450.

Zhang J, Xu YM, Wang WM, Liu YQ. Experimental study on anti-tumor effect of extractive from Celastrus orbiculatus in vivo. China J Chin Mater Med (Chin) 2006;31:1514–1516.

Zan K, Chen XQ, Wang Q, Cao L. Chemical constituents in stem of Celastrus orbiculatus. Chin Tradit Herb Drugs (Chin) 2007;38:1455–1457.

Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis: correlation in invasive breast cancer. N Engl J Med 1991;324:1–8.

Grant DS, Kleinman HK. Regulation of capillary formation by laminin and other components of the extracellular matrix. EXS 1997;79:317–333.

Ng IO, Poon RT, Lee JM, Fan ST, Ng M, Tso WK. Microvessel density, vascular endothelial growth factor and its receptors Flt-1 and Flk-1/KDR in hepatocellular carcinoma. Am J Clin Pathol 2001;116:838–845.

Folkman J. Fighting cancer by attacking its blood supply. Sci Am 1996;275:150–154.

Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology 2005;69 (Suppl 3):4–10.

Komaki H, Tanaka Y, Yazawa K, Takagi H, Ando A, Nagata Y, et al. Antitumor activity of brasilicardin A, a novel terpenoid antibiotic from Nocardia brasiliensis. J Antibiot (Tokyo) 2000;53:75–77.

Sethi G, Ahn KS, Pandey MK, Aggarwal BB. Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-κBregulated gene products and TAK1-mediated NF-κB activation. Blood 20 2007;109:2727–2735

Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 1996;2:1096–1103.

Shibata S, Okano S, Yonemitsu Y, Onimaru M, Sata S, Nagata-Takeshita H, et al. Induction of efficient antitumor immunity using dendritic cells activated by recombinant Sendai virus and its modulation by exogenous IFN-beta gene. J Immunol 2006;177:3564–3576.

Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245–252.

Qian YY, Zhang H, Yuan L, Hou Y, Liu YQ. Enhancement of extracts from Celastrus orbiculatus on maturation and function of dendritic cells in vitro and in vivo. Chin Herb Med (Chin) 2010;2:195–203.

Wu C. Integrin-linked kinase and PINCH: partners in regulation of cell-extracellular matrix interaction and signal transduction. J Cell Sci 1999;112:4485–4489.

Huie CW. A review of modern sample-preparation techniques for the extraction and analysis of medicinal plants. Anal Bioanal Chem 2002;373:23–30.

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