Eriocalyxin B, a natural diterpenoid, inhibited VEGF-induced angiogenesis and diminished angiogenesis-dependent breast tumor growth by suppressing VEGFR-2 signaling
Zhou, Xunian1,2; Yue, Grace Gar-Lee2,3; Liu, Minghua1; Zuo, Zhili4; Lee, Julia Kin-Ming; Li, Mingyue1; Tsui, Stephen Kwok-Wing1; Fung, Kwok-Pui1,2,3; Sun, Handong4; Pu, Jianxin4; Lau, Clara Bik-San2,3
2016-12-13
Source PublicationONCOTARGET
Volume7Issue:50Pages:82820-82835
AbstractEriocalyxin B (EriB), a natural ent-kaurane diterpenoid isolated from the plant Isodon eriocalyx var. laxiflora, has emerged as a promising anticancer agent. The effects of EriB on angiogenesis were explored in the present study. Here we demonstrated that the subintestinal vein formation was significantly inhibited by EriB treatment (10, 15 mu M) in zebrafish embryos, which was resulted from the alteration of various angiogenic genes as shown in transcriptome profiling. In human umbilical vein endothelial cells, EriB treatment (50, 100 nM) could significantly block vascular endothelial growth factors (VEGF)-induced cell proliferation, tube formation, cell migration and cell invasion. Furthermore, EriB also caused G1 phase cell cycle arrest which was correlated with the down-regulation of the cyclin D1 and CDK4 leading to the inhibition of phosphorylated retinoblastoma protein expression. Investigation of the signal transduction revealed that EriB inhibited VEGF-induced phosphorylation of VEGF receptor-2 via the interaction with the ATP-binding sites according to the molecular docking simulations. The suppression of VEGFR-2 downstream signal transduction cascades was also observed. EriB was showed to inhibit new blood vessel formation in Matrigel plug model and mouse 4T1 breast tumor model. EriB (5 mg/kg/day) treatment was able to decrease tumor vascularization and suppress tumor growth and angiogenesis. Taken together, our findings suggested that EriB is a novel inhibitor of angiogenesis through modulating VEGFR-2 signaling pathway, which could be developed as a promising anti-angiogenic agent for treatment of angiogenesis-related human diseases, such as cancer.
KeywordEriocalyxin b Angiogenesis Vascular Endothelial Growth Factor (Vegf) Vascular Endothelial Growth Factor Receptor 2(Vegfr-2) Breast Cancer
DOI10.18632/oncotarget.12652
Indexed BySCI
Language英语
WOS IDWOS:000391352800072
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/33806
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China
2.Chinese Univ Hong Kong, Inst Chinese Med, Shatin, Hong Kong, Peoples R China
3.Chinese Univ Hong Kong, State Key Lab Phytochem & Plant Resources West Ch, Shatin, Hong Kong, Peoples R China
4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Yunnan, Peoples R China
Recommended Citation
GB/T 7714
Zhou, Xunian,Yue, Grace Gar-Lee,Liu, Minghua,et al. Eriocalyxin B, a natural diterpenoid, inhibited VEGF-induced angiogenesis and diminished angiogenesis-dependent breast tumor growth by suppressing VEGFR-2 signaling[J]. ONCOTARGET,2016,7(50):82820-82835.
APA Zhou, Xunian.,Yue, Grace Gar-Lee.,Liu, Minghua.,Zuo, Zhili.,Lee, Julia Kin-Ming.,...&Lau, Clara Bik-San.(2016).Eriocalyxin B, a natural diterpenoid, inhibited VEGF-induced angiogenesis and diminished angiogenesis-dependent breast tumor growth by suppressing VEGFR-2 signaling.ONCOTARGET,7(50),82820-82835.
MLA Zhou, Xunian,et al."Eriocalyxin B, a natural diterpenoid, inhibited VEGF-induced angiogenesis and diminished angiogenesis-dependent breast tumor growth by suppressing VEGFR-2 signaling".ONCOTARGET 7.50(2016):82820-82835.
Files in This Item: Download All
File Name/Size DocType Version Access License
12652-189796-3-PB.pd(13632KB)期刊论文作者接受稿开放获取CC BY-NC-SAView Download
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Zhou, Xunian]'s Articles
[Yue, Grace Gar-Lee]'s Articles
[Liu, Minghua]'s Articles
Baidu academic
Similar articles in Baidu academic
[Zhou, Xunian]'s Articles
[Yue, Grace Gar-Lee]'s Articles
[Liu, Minghua]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Zhou, Xunian]'s Articles
[Yue, Grace Gar-Lee]'s Articles
[Liu, Minghua]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: 12652-189796-3-PB.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.