2010 年 33 巻 4 号 p. 622-630
α-Chaconine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation, migration, invasion, and inducing apoptosis of tumor cells. However, the effect of α-chaconine on tumor angiogenesis remains unclear. In the present study, we examined the effect of α-chaconine on angiogenesis in vitro. Data demonstrated that α-chaconine inhibited proliferation of bovine aortic endothelial cells (BAECs) in a dose-dependent manner. When treated with non-toxic doses of α-chaconine, cell migration, invasion and tube formation were markedly suppressed. Furthermore, α-chaconine reduced the expression and activity of matrix metalloproteinase-2 (MMP-2), which is involved in angiogenesis. Our biochemical assays indicated that α-chaconine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK) and p38. In addition, α-chaconine significantly increased the cytoplasmic level of inhibitors of κBα (IκBα) and decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that α-chaconine could inhibit NF-κB activity. Furthermore, the treatment of inhibitors specific for JNK (SP600125), PI3K (LY294002) or NF-κB (pyrrolidine dithiocarbamate) to BAECs reduced tube formation. Taken together, the results suggested that α-chaconine inhibited migration, invasion and tube formation of BAECs by reducing MMP-2 activities, as well as JNK and PI3K/Akt signaling pathways and inhibition of NF-κB activity. These findings reveal a new therapeutic potential for α-chaconine on anti-angiogenic therapy.
