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

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Yan KH, Lee LM, Yan SH, Huang HC, Li CC, Lin HT, Chen PS

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

Chem Biol Interact. 2013 May 25;203(3):580-7. doi: 10.1016/j.cbi.2013.03.016. Epub 2013 Apr 6.

PubMed ID

23566884 [ View in PubMed

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Abstract

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-kappaB), which suggests that tomatidine inhibits NF-kappaB activity. Furthermore, the treatment of inhibitors specific for PI3K/Akt (LY294002), ERK (U0126), or NF-kappaB (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-kappaB activity. These findings demonstrate a new therapeutic potential for tomatidine in anti-metastatic therapy.

DrugBank Data that Cites this Article

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
LY-294002	Experimental	MMP2	4313	downregulated	2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one results in decreased expression of MMP2 mRNA	16q12.2
LY-294002	Experimental	MMP9	4318	downregulated	2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one results in decreased expression of MMP9 mRNA	20q13.12