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.