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Title: Platycodin D inhibits tumor growth by antiangiogenic activity via blocking VEGFR2-mediated signaling pathway

Abstract

Platycodin D (PD) is an active component mainly isolated from the root of Platycodon grandiflorum. Recent studies proved that PD exhibited inhibitory effect on proliferation, migration, invasion and xenograft growth of diverse cancer cell lines. However, whether PD is suppressive for angiogenesis, an important hallmark in cancer development, remains unknown. Here, we found that PD could dose-dependently inhibit human umbilical vein endothelial cell (HUVEC) proliferation, motility, migration and tube formation. PD also significantly inhibited angiogenesis in the chick embryo chorioallantoic membrane (CAM). Moreover, the antiangiogenic activity of PD contributed to its in vivo anticancer potency shown in the decreased microvessel density and delayed growth of HCT-15 xenograft in mice with no overt toxicity. Western blot analysis indicated that PD inhibited the phosphorylation of VEGFR2 and its downstream protein kinase including PLCγ1, JAK2, FAK, Src, and Akt in endothelial cells. Molecular docking simulation showed that PD formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. The present study firstly revealed the high antiangiogenic activity and the underlying molecular basis of PD, suggesting that PD may be a potential antiangiogenic agent for angiogenesis-related diseases. - Highlights: • Platycodin D inhibits HUVEC proliferation, motility, migration and tubemore » formation. • Platycodin D inhibits the angiogenesis in chick embryo chorioallantoic membrane. • Platycodin D suppresses the angiogenesis and growth of HCT-15 xenograft in mice. • Platycodin D inhibits the phosphorylation of VEGFR2 and downstream kinases in HUVEC.« less

Authors:
; ; ; ;  [1];  [2]; ;  [1];  [1];  [1]
  1. Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China)
  2. Department of Pharmacy, Shanghai Institute of Health Sciences and Health School Attached to SJTU-SM, 279 Zhouzhu Road, Shanghai 201318 (China)
Publication Date:
OSTI Identifier:
22439915
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 281; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; ATP; DOSES; EMBRYOS; FETAL MEMBRANES; HYDROGEN; IN VIVO; MICE; NEOPLASMS; PHOSPHORYLATION; PHOSPHOTRANSFERASES; TOXICITY

Citation Formats

Luan, Xin, Gao, Yun-Ge, Guan, Ying-Yun, Xu, Jian-Rong, Lu, Qin, Zhao, Mei, Liu, Ya-Rong, Liu, Hai-Jun, Fang, Chao, and Chen, Hong-Zhuan. Platycodin D inhibits tumor growth by antiangiogenic activity via blocking VEGFR2-mediated signaling pathway. United States: N. p., 2014. Web. doi:10.1016/J.TAAP.2014.09.009.
Luan, Xin, Gao, Yun-Ge, Guan, Ying-Yun, Xu, Jian-Rong, Lu, Qin, Zhao, Mei, Liu, Ya-Rong, Liu, Hai-Jun, Fang, Chao, & Chen, Hong-Zhuan. Platycodin D inhibits tumor growth by antiangiogenic activity via blocking VEGFR2-mediated signaling pathway. United States. https://doi.org/10.1016/J.TAAP.2014.09.009
Luan, Xin, Gao, Yun-Ge, Guan, Ying-Yun, Xu, Jian-Rong, Lu, Qin, Zhao, Mei, Liu, Ya-Rong, Liu, Hai-Jun, Fang, Chao, and Chen, Hong-Zhuan. 2014. "Platycodin D inhibits tumor growth by antiangiogenic activity via blocking VEGFR2-mediated signaling pathway". United States. https://doi.org/10.1016/J.TAAP.2014.09.009.
@article{osti_22439915,
title = {Platycodin D inhibits tumor growth by antiangiogenic activity via blocking VEGFR2-mediated signaling pathway},
author = {Luan, Xin and Gao, Yun-Ge and Guan, Ying-Yun and Xu, Jian-Rong and Lu, Qin and Zhao, Mei and Liu, Ya-Rong and Liu, Hai-Jun and Fang, Chao and Chen, Hong-Zhuan},
abstractNote = {Platycodin D (PD) is an active component mainly isolated from the root of Platycodon grandiflorum. Recent studies proved that PD exhibited inhibitory effect on proliferation, migration, invasion and xenograft growth of diverse cancer cell lines. However, whether PD is suppressive for angiogenesis, an important hallmark in cancer development, remains unknown. Here, we found that PD could dose-dependently inhibit human umbilical vein endothelial cell (HUVEC) proliferation, motility, migration and tube formation. PD also significantly inhibited angiogenesis in the chick embryo chorioallantoic membrane (CAM). Moreover, the antiangiogenic activity of PD contributed to its in vivo anticancer potency shown in the decreased microvessel density and delayed growth of HCT-15 xenograft in mice with no overt toxicity. Western blot analysis indicated that PD inhibited the phosphorylation of VEGFR2 and its downstream protein kinase including PLCγ1, JAK2, FAK, Src, and Akt in endothelial cells. Molecular docking simulation showed that PD formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. The present study firstly revealed the high antiangiogenic activity and the underlying molecular basis of PD, suggesting that PD may be a potential antiangiogenic agent for angiogenesis-related diseases. - Highlights: • Platycodin D inhibits HUVEC proliferation, motility, migration and tube formation. • Platycodin D inhibits the angiogenesis in chick embryo chorioallantoic membrane. • Platycodin D suppresses the angiogenesis and growth of HCT-15 xenograft in mice. • Platycodin D inhibits the phosphorylation of VEGFR2 and downstream kinases in HUVEC.},
doi = {10.1016/J.TAAP.2014.09.009},
url = {https://www.osti.gov/biblio/22439915}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 281,
place = {United States},
year = {Sat Nov 15 00:00:00 EST 2014},
month = {Sat Nov 15 00:00:00 EST 2014}
}