Anti-angiogenic activity of Eriocalyxin B, a natural diterpenoid, by targeting VEGFR-2 signaling pathway
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AbstractAngiogenesis is the formation of new capillaries from existing blood vessels, which served as an essential requirement for tumor growth. Eriocalyxin B (EriB), a natural diterpenoid isolated from Isodon eriocalyx Dunn, exerts multiple anti­tumor activities [1, 2]. Thus, the aim of the present investigation was to determine the anti-angiogenic effect of EriB.

The transgenic zebrafish Tg(fli1:EGFP)y1 which expressed enhanced Green Fluorescent Proteins (eGFP) was used to determine the inhibitory effect of EriB (10, 15 μM) on the formation of sub­intestinal vessels. Then the genome wide mRNA expression profiling of zebrafish after EriB treatment was applied to find out the novel angiogenic genes (e.g. kdr, pcdh15b, cdkn1a, loxl1, etc.). Our results in human umbilical vein endothelial cells revealed that EriB treatment (50, 100 nM) could significantly suppress vascular endothelial growth factor induced in vitro angiogenesis. Flow cytometry analysis demonstrated that EriB (100 nM) could induce cell cycle arrest at G1 phase via the interference of cyclinD1/CDK4/pRb pathway. Additionally, the suppression of VEGFR-2 signaling was also observed, which resulted from the competitive interaction with the VEGFR-2 ATP-binding site based on molecular docking anaylsis. Furthermore, we also find out that EriB (20 μM) inhibited new blood vessel formation in Matrigel plug model and EriB treatment (5 mg/kg/day) was able to decrease tumor vascularization and suppress tumor growth in 4T1 breast tumor model.

Taken together, our findings suggested that EriB is a novel anti­angiogenic agent through the suppression of VEGFR-2 signaling pathway, which could be developed as a promising anti-angiogenic agent for treatment of cancer.
All Author(s) ListXunian Zhou, Grace Gar-Lee Yue, Minghua Liu, Zhili Zuo, Julia Kin-Ming Lee, Mingyue Li, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Handong Sun, Jianxin Pu, Clara Bik-San Lau
Name of ConferenceThe 12th International Postgraduate Symposium on Chinese Medicine
Start Date of Conference12/08/2016
End Date of Conference12/08/2016
Place of ConferenceHong Kong Convention and Exhibition Centre
Country/Region of ConferenceHong Kong
LanguagesEnglish-United States

Last updated on 2018-18-01 at 03:07