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ECB-ART-39306
Int J Cancer 2005 May 10;1146:843-53. doi: 10.1002/ijc.20804.
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Philinopside A, a novel marine-derived compound possessing dual anti-angiogenic and anti-tumor effects.

Tong Y , Zhang X , Tian F , Yi Y , Xu Q , Li L , Tong L , Lin L , Ding J .


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Philinopside A is a novel sulfated saponin isolated from the sea cucumber, Pentacta quadrangulari. The effects of philinopside A on angiogenesis and tumor growth were assessed in a series of models in vitro and in vivo. Our results demonstrated that philinopside A significantly inhibited the proliferation, migration and tube formation of human microvascular endothelial cells (HMECs) in a dose-dependent manner, with average IC(50) values of 1.4 +/- 0.17, 0.89 +/- 0.23 and 0.98 +/- 0.19 microM, respectively. Rat aortas culture assay provides a close imitation of in vivo angiogenesis process and 2-10 microM philinopside A suppressed the formation of new microvessels in cultured rat aortas. Philinopside A 2-10 nmol/egg obviously inhibited angiogenesis in chick embryo chorioallantoic membrane assay. In addition, philinopside A manifested strong anti-tumor activities both in vitro and in vivo. Through immunofluorescent analysis, we found the compound reduced mouse sarcoma 180 tumor volume by inducing apoptosis of tumor and tumor-associated endothelial cells. An examination of the effects of philinopside A on the angiogenesis-related receptor tyrosine kinases (RTKs) showed that philinopside A broadly inhibited all tested RTKs, including vascular endothelial growth factor (VEGF) receptor, fibroblast growth factor (FGF) receptor-1, platelet-derived growth factor (PDGF) receptor-beta and epithelial growth factor (EGF) receptor, with IC(50) values ranging from 2.6-4.9 microM. These results suggest that philinopside A is a promising anti-cancer agent that possesses dual cytotoxic and anti-angiogenic effects that were at least partly due to its inhibitory effects on RTKs.

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Genes referenced: fgf LOC100887844 LOC100889782 LOC100893812 LOC105441151 LOC115922368 vegfc