Raddeanin A, a triterpenoid saponin isolated from Anemone raddeana, suppresses the angiogenesis and growth of human colorectal tumor by inhibiting VEGFR2 signaling

Raddeanin A (RA) is an active triterpenoid saponin from a traditional Chinese medicinal herb, Anemone raddeana Regel. It was previously reported that RA possessed attractive antitumor activity through inhibiting proliferation and inducing Apoptosis of multiple Cancer cells. However, whether RA can inhibit angiogenesis, an essential step in Cancer development, remains unknown. In this study, we found that RA could significantly inhibit human umbilical vein endothelial cell (HUVEC) proliferation, motility, migration, and tube formation. RA also dramatically reduced angiogenesis in chick embryo chorioallantoic membrane (CAM), restrained the trunk angiogenesis in zebrafish, and suppressed angiogenesis and growth of human HCT-15 colorectal Cancer xenograft in mice. Western blot assay showed that RA suppressed VEGF-induced phosphorylation of VEGFR2 and its downstream protein kinases including PLCγ1, JAK2, FAK, Src, and Akt. Molecular docking simulation indicated that RA formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. Our study firstly provides the evidence that RA has high antiangiogenic potency and explores its molecular basis, demonstrating that RA is a potential agent or lead candidate for antiangiogenic Cancer therapy.

Anemone raddeana; Colorectal tumor; Raddeanin A; Tumor angiogenesis; VEGFR2; Zebrafish.