Antiangiogenic Properties of Caudatin In vitro and In vivo by Suppression of VEGF‑VEGFR2‑AKT/FAK Signal Axis

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2017 Oct 10

PMID 28990104

Citations 7

Authors

Xinzhi Wang

Xiaoting Fu

Shijun Zhao

Xiaoyan Fu

Huifang Zhang

Lurong Shao

Gang Li

Cundong Fan

Affiliations

Soon will be listed here.

Abstract

Tumor angiogenesis provides essential nutrients and oxygen to the tumor microenvironment, which is important in tumor growth, progression and metastasis. Inhibition of tumor angiogenesis represents one of the most promising strategies in tumor therapy. The authors previously demonstrated that caudatin, one species of C‑21 steroidal from Cynanchum auriculatum (C. auriculatum), effectively inhibits human glioma growth in vitro and in vivo through triggering cell cycle arrest and apoptosis. However, little information regarding the antiangiogenic properties of caudatin in human glioma is available. Based on the author's previous study, the antiangiogenic effect of caudatin against human glioma was explored, and the underlying mechanism was investigated. The results suggested that caudatin treatment significantly inhibited HUVEC human umbilical vein endothelial cell proliferation, blocked the HUVECs migration, invasion and capillary‑like tube formation by disturbing the vascular endothelial growth factor (VEGF)‑VEGFR2‑protein kinase B (AKT)/focal adhesion kinase (FAK) signal axis. Notably, caudatin treatment abolished the glioma cell growth by suppression of the in vivo angiogenesis, which involved FAK and AKT dephosphorylation and inhibition of VEGF expression. The findings validated the antiangiogenic potential of caudatin in hunting human glioma.

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References

Shen T, Park A, Alcaraz A, Peng X, Jang I, Koni P . Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. J Cell Biol. 2005; 169(6):941-52. PMC: 2171636. DOI: 10.1083/jcb.200411155. View

Wang Y, Yang B, Zhang R, Wei E . [Inhibitive effect of C-21 steroidal glycosides of Cynanchum auriculatum on rat glioma cells in vitro]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2011; 40(4):402-7. DOI: 10.3785/j.issn.1008-9292.2011.04.010. View

Berz D, Wanebo H . Targeting the growth factors and angiogenesis pathways: small molecules in solid tumors. J Surg Oncol. 2011; 103(6):574-86. DOI: 10.1002/jso.21776. View

Luo Y, Sun Z, Li Y, Liu L, Cai X, Li Z . Caudatin inhibits human hepatoma cell growth and metastasis through modulation of the Wnt/β-catenin pathway. Oncol Rep. 2013; 30(6):2923-8. DOI: 10.3892/or.2013.2749. View

Pyun B, Choi S, Lee Y, Kim T, Min J, Kim Y . Capsiate, a nonpungent capsaicin-like compound, inhibits angiogenesis and vascular permeability via a direct inhibition of Src kinase activity. Cancer Res. 2008; 68(1):227-35. DOI: 10.1158/0008-5472.CAN-07-2799. View

Mitra S, Mikolon D, Molina J, Hsia D, HANSON D, Chi A . Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors. Oncogene. 2006; 25(44):5969-84. DOI: 10.1038/sj.onc.1209588. View

Li X, Zhang M, Xiang C, Qin Y, He J, Li B . [C21 steroids from roots of Cynanchum otophyllum]. Zhongguo Zhong Yao Za Zhi. 2014; 39(8):1450-6. View

Ferrara N . Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004; 25(4):581-611. DOI: 10.1210/er.2003-0027. View

Fan C, Zheng W, Fu X, Li X, Wong Y, Chen T . Enhancement of auranofin-induced lung cancer cell apoptosis by selenocystine, a natural inhibitor of TrxR1 in vitro and in vivo. Cell Death Dis. 2014; 5:e1191. PMC: 4001298. DOI: 10.1038/cddis.2014.132. View

10.

Peng Y, Ding Y . Pharmacokinetics and tissue distribution study of caudatin in normal and diethylnitrosamine-induced hepatocellular carcinoma model rats. Molecules. 2015; 20(3):4225-37. PMC: 6272519. DOI: 10.3390/molecules20034225. View

11.

Holopainen T, Bry M, Alitalo K, Saaristo A . Perspectives on lymphangiogenesis and angiogenesis in cancer. J Surg Oncol. 2011; 103(6):484-8. DOI: 10.1002/jso.21808. View

12.

Fresno Vara J, Casado E, de Castro J, Cejas P, Belda-Iniesta C, Gonzalez-Baron M . PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 2004; 30(2):193-204. DOI: 10.1016/j.ctrv.2003.07.007. View

13.

Holmqvist K, Cross M, Rolny C, Hagerkvist R, Rahimi N, Matsumoto T . The adaptor protein shb binds to tyrosine 1175 in vascular endothelial growth factor (VEGF) receptor-2 and regulates VEGF-dependent cellular migration. J Biol Chem. 2004; 279(21):22267-75. DOI: 10.1074/jbc.M312729200. View

14.

Wang L, Chen H, Ma Y, Huang X, Geng C, Zhang X . Design, synthesis and biological evaluation of caudatin analogs as potent hepatitis B virus inhibitors. Med Chem. 2014; 11(2):165-79. DOI: 10.2174/1573406410666140902111326. View

15.

Fu X, Zhang S, Wang K, Yang M, Fan C, Sun B . Caudatin Inhibits Human Glioma Cells Growth Through Triggering DNA Damage-Mediated Cell Cycle Arrest. Cell Mol Neurobiol. 2015; 35(7):953-9. PMC: 11486222. DOI: 10.1007/s10571-015-0190-x. View

16.

Josko J, Mazurek M . Transcription factors having impact on vascular endothelial growth factor (VEGF) gene expression in angiogenesis. Med Sci Monit. 2004; 10(4):RA89-98. View

17.

Wang Y, Zhang S, Lu H, Yang B, Ye L, Zhang R . A C 21 -Steroidal Glycoside Isolated from the Roots of Cynanchum auriculatum Induces Cell Cycle Arrest and Apoptosis in Human Gastric Cancer SGC-7901 Cells. Evid Based Complement Alternat Med. 2014; 2013:180839. PMC: 3880714. DOI: 10.1155/2013/180839. View

18.

Bolat F, Haberal N, Tunali N, Aslan E, Bal N, Tuncer I . Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor 1 alpha (HIF-1alpha), and transforming growth factors beta1 (TGFbeta1) and beta3 (TGFbeta3) in gestational trophoblastic disease. Pathol Res Pract. 2009; 206(1):19-23. DOI: 10.1016/j.prp.2009.07.017. View

19.

Ren W, Qiao Z, Wang H, Zhu L, Zhang L . Flavonoids: promising anticancer agents. Med Res Rev. 2003; 23(4):519-34. DOI: 10.1002/med.10033. View

20.

Zhu L, Hou Y, Zhao M, Yang M, Fu X, Sun J . Caudatin induces caspase-dependent apoptosis in human glioma cells with involvement of mitochondrial dysfunction and reactive oxygen species generation. Cell Biol Toxicol. 2016; 32(4):333-45. DOI: 10.1007/s10565-016-9338-9. View