Philinopside a, a novel marine‐derived compound possessing dual anti‐angiogenic and anti‐tumor effects
Open Access
- 11 January 2005
- journal article
- carcinogenesis
- Published by Wiley in International Journal of Cancer
- Vol. 114 (6), 843-853
- https://doi.org/10.1002/ijc.20804
Abstract
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 IC50 values of 1.4 ± 0.17, 0.89 ± 0.23 and 0.98 ± 0.19 μM, respectively. Rat aortas culture assay provides a close imitation of in vivo angiogenesis process and 2–10 μM 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-β and epithelial growth factor (EGF) receptor, with IC50 values ranging from 2.6–4.9 μM. 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.Keywords
This publication has 38 references indexed in Scilit:
- Angiogenesis as a target for cancer therapyHematology/Oncology Clinics of North America, 2002
- Tumor angiogenesis as a therapeutic targetDrug Discovery Today, 2001
- Monoclonal antibody strategies to block angiogenesisDrug Discovery Today, 2001
- VEGF: an update on biological and therapeutic aspectsCurrent Opinion in Biotechnology, 2000
- Inhibition of tumor angiogenesis by synthetic receptor tyrosine kinase inhibitorsDrug Discovery Today, 2000
- Expression of the angiogenic factors, basic fibroblast growth factor and vascular endothelial growth factor, in the ovary.Journal of Animal Science, 1998
- Receptor tyrosine kinases as targets for inhibition of angiogenesisDrug Discovery Today, 1997
- Expression of vascular endothelial growth factor (VEGF) during folliculogenesis and corpus luteum formation in the human ovaryGynecological Endocrinology, 1997
- Particle-mediated gene transfer with transforming growth factor-beta1 cDNAs enhances wound repair in rat skin.JCI Insight, 1996
- Angiogenesis in cancer, vascular, rheumatoid and other diseaseNature Medicine, 1995