| 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
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| 2016-12-13 | |
| 发表期刊 | ONCOTARGET
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| 卷号 | 7期号:50页码:82820-82835 |
| 摘要 | Eriocalyxin 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. |
| 关键词 | Eriocalyxin b Angiogenesis Vascular Endothelial Growth Factor (Vegf) Vascular Endothelial Growth Factor Receptor 2(Vegfr-2) Breast Cancer |
| DOI | 10.18632/oncotarget.12652 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000391352800072 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/33806 |
| 专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
| 作者单位 | 1.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 |
| 推荐引用方式 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. |
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