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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2014

01-04-2014 | Original Article

Paris Saponin II suppresses the growth of human ovarian cancer xenografts via modulating VEGF-mediated angiogenesis and tumor cell migration

Authors: Xue Xiao, Mei Yang, Jianguo Xiao, Juan Zou, Qin Huang, Kaixuan Yang, Bo Zhang, Fan Yang, Shanling Liu, He Wang, Peng Bai

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2014

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Abstract

Purpose

Paris Saponin II (PSII) is an active component of Rhizoma Paridis—an essential ingredient in traditional Chinese herbal medicines. PSII can induce cytotoxic effects in cancer cells and inhibit ovarian cancer growth. Since pathological angiogenesis (henceforth, angiogenesis) is often associated with gynecological cancers, here, we investigated whether PSII renders effects on angiogenesis and examined possible molecular mechanisms underlying the effects of PSII.

Methods

The effects of PSII on the biofunctions of endothelial cells (EC), the crucial components of blood vessels, were examined by standardized angiogenesis in vitro and ex vivo assays, Western blot analysis, ELISA, and kinase assay. Angiogenesis in a xenograft mouse model of ovarian cancer was evaluated by color Doppler ultrasound and immunohistochemistry.

Results

PSII exerted marked inhibitory effect on the growth of VEGF-stimulated human umbilical vein endothelial cells in a dose–time-dependent manner, inhibited cell’s motility, and interfered with tubulogenesis. PSII also blocked microvessel outgrowth in a rat aortic ring assay and compromised angiogenesis in a mouse model of ovarian carcinoma using either SKOV3 or HOC-7 cell lines. VEGF levels in PSII-treated EC and tumor cells were reduced. In EC, PSII blocked the activation of VEGFR2 in dose-dependent manner leading to the reduction of VEGF-induced phosphorylation on several intracellular pro-angiogenic kinase, including the extracellular signal-related kinase, Src family kinase, focal adhesion kinase, and AKT kinase.

Conclusions

The results provided the first insight into the anti-angiogenesis properties of Saponin family in solid tumors and suggested a promising therapeutic potential of PSII in the ovarian cancer treatment.
Appendix
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Metadata
Title
Paris Saponin II suppresses the growth of human ovarian cancer xenografts via modulating VEGF-mediated angiogenesis and tumor cell migration
Authors
Xue Xiao
Mei Yang
Jianguo Xiao
Juan Zou
Qin Huang
Kaixuan Yang
Bo Zhang
Fan Yang
Shanling Liu
He Wang
Peng Bai
Publication date
01-04-2014
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2014
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-014-2408-x

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