Tomatidine inhibits invasion of human lung adenocarcinoma cell A549 by reducing matrix metalloproteinases expression

doi:10.1016/j.cbi.2013.03.016

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標題:	Tomatidine inhibits invasion of human lung adenocarcinoma cell A549 by reducing matrix metalloproteinases expression
作者:	Yan, Kun-Huang Lee, Liang-Ming Yan, Shao-Han Huang, Hsiang-Ching Li, Chia-Chen Lin, Hui-Ting Chen, Pin-Shern
貢獻者:	生物科技系
關鍵字:	Tomatidine Invasion Matrix Metalloproteinase
日期:	2013-05
上傳時間:	2014-05-26 10:50:21 (UTC+8)
出版者:	Elsevier Ireland Ltd
摘要:	Tomatidine is an aglycone of glycoalkaloid tomatine in tomato. Tomatidine is found to possess anti-inflammatory properties and may serve as a chemosensitizer in multidrug-resistant tumor cells. However, the effect of tomatidine on cancer cell metastasis remains unclear. This study examines the effect of tomatidine on the migration and invasion of human lung adenocarcinoma A549 cell in vitro. The data demonstrates that tomatidine does not effectively inhibit the viability of A549 cells. When treated with non-toxic doses of tomatidine, cell invasion is markedly suppressed by Boyden chamber invasion assay, while cell migration is not affected. Tomatidine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1). The immunoblotting assays indicate that tomatidine is very effective in suppressing the phosphorylation of Akt and extracellular signal regulating kinase (ERK). In addition, tomatidine significantly decreases the nuclear level of nuclear factor kappa B (NF-kappa B), which suggests that tomatidine inhibits NF-kappa B activity. Furthermore, the treatment of inhibitors specific for PI3K/Akt (LY294002), ERK (U0126), or NF-kappa B (pyrrolidine dithiocarbamate) to A549 cells reduced cell invasion and MMP-2/9 expression. The results suggest that tomatidine inhibits the invasion of A549 cells by reducing the expression of MMPs. It also inhibits ERK and Akt signaling pathways and NF-kappa B activity. These findings demonstrate a new therapeutic potential for tomatidine in anti-metastatic therapy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
關聯:	Chemico-Biological Interactions, v.203 n.3, pp.580-587
显示于类别:	[生物科技系(所)] 期刊論文

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