Philinopside A, a novel marine-derived compound possessing dual anti-angiogenic and anti-tumor effects.
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.
Tong
Yunguang
Y
Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
Zhang
Xiongwen
X
Tian
Fang
F
Yi
Yanghua
Y
Xu
Qiangzhi
Q
Li
Ling
L
Tong
Linjiang
L
Lin
Liping
L
Ding
Jian
J
D000818:Animals; D001011:Aorta; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D042783:Endothelial Cells; D006133:Growth Substances / Q000494:pharmacology; D051379:Mice; D009389:Neovascularization, Pathologic; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects* / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D012509:Sarcoma / Q000473:pathology; D012616:Sea Cucumbers / Q000737:chemistry
D006133:Growth Substances; D012503:Saponins; C500379:philinopside A; D020794:Receptor Protein-Tyrosine Kinases