α-Chaconine inhibits angiogenesis in vitro by reducing matrix metalloproteinase-2

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標題:	α-Chaconine inhibits angiogenesis in vitro by reducing matrix metalloproteinase-2
作者:	Ming-Kun LU Pei-Hsieng CHEN Yuan-Wei SHIH Ya-Ting CHANG En-Tze HUANG Cheng-Ruei LIU Pin-Shern CHEN
貢獻者:	生物科技系
關鍵字:	α-chaconine angiogenesis matrix metalloproteinase-2 c-Jun-N-terminal kinase Akt neuclear factor kappa B
日期:	2010-04
上傳時間:	2012-03-30 15:17:53 (UTC+8)
摘要:	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.
關聯:	Biol. Pharm. Bull.33(4)：p.622-630
顯示於類別:	[生物科技系(所)] 期刊論文

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