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

Kun Huang Yan, Liang Ming Lee, Shao Han Yan, Hsiang Ching Huang, Chia Chen Li, Hui Ting Lin, Pin Shern Chen

Research output: Contribution to journalArticle

29 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)580-587
Number of pages8
JournalChemico-Biological Interactions
Volume203
Issue number3
DOIs
Publication statusPublished - May 25 2013

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Matrix Metalloproteinases
NF-kappa B
Phosphotransferases
Matrix Metalloproteinase 2
A549 Cells
Adenocarcinoma of lung
tomatidine
Tomatine
Assays
Cell Migration Assays
Cells
Phosphorylation
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 9
Lycopersicon esculentum
Phosphatidylinositol 3-Kinases
Immunoblotting
Cysteine
Tumors

Keywords

  • Invasion
  • Matrix metalloproteinase
  • Tomatidine

ASJC Scopus subject areas

  • Toxicology

Cite this

Tomatidine inhibits invasion of human lung adenocarcinoma cell A549 by reducing matrix metalloproteinases expression. / Yan, Kun Huang; Lee, Liang Ming; Yan, Shao Han; Huang, Hsiang Ching; Li, Chia Chen; Lin, Hui Ting; Chen, Pin Shern.

In: Chemico-Biological Interactions, Vol. 203, No. 3, 25.05.2013, p. 580-587.

Research output: Contribution to journalArticle

Yan, Kun Huang ; Lee, Liang Ming ; Yan, Shao Han ; Huang, Hsiang Ching ; Li, Chia Chen ; Lin, Hui Ting ; Chen, Pin Shern. / Tomatidine inhibits invasion of human lung adenocarcinoma cell A549 by reducing matrix metalloproteinases expression. In: Chemico-Biological Interactions. 2013 ; Vol. 203, No. 3. pp. 580-587.
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