Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect

Abstract

Aims This study examined the in vitro and in vivo angiogenic effects of norcantharidin (NCTD), a synthetic, small-molecule antitumor compound. Main methods Syngeneic colorectal adenocarcinoma CT26 cells were implanted in mice to examine the effect of NCTD on VEGF production and renal and hepatic toxicity. Human umbilical endothelial cells (HUVECs) were used to examine the in vitro effect of NCTD on viability, chemotaxis, vascular network tube formation, adhesive ability, anoikis, and mitogen-activated protein kinase (MAPK) signaling. A protein array was used for analysis of angiogenic factors released from NCTD-treated HUVECs. Key findings NCTD suppressed plasma VEGF levels of tumor-bearing mice, without renal or hepatic toxicity. In vitro, NCTD inhibited viability of normal HUVECs to a lesser extent than CT26 cancer cells. At concentrations less than those inhibiting 50% of the cells, NCTD inhibited migration and capillary-like tube formation of HUVECs. The anti-angiogenic effect of NCTD was accompanied by anoikis, down-regulation of integrin β1, and breakdown of vimentin. NCTD decreased MAPK expression of phosphorylated (p)-JNK and p-ERK. P-P38 expression or P38 inhibitor SB203580 did not impair the effect of NCTD on viability or adhesion of HUVECs. In addition, NCTD inhibited the release of pro-angiogenic factors from HUVECs, but not from CT26 cells. Significance NCTD is a synthetic, small-molecule compound possessing anti-angiogenetic activity with potential use in anti-cancer therapy as an anti-metastatic and anti-angiogenic agent.