Suppression of 12-O-Tetradecanoylphorbol-13-Acetate-Induced MCF-7 Breast Adenocarcinoma Cells Invasion/Migration by α-Tomatine Through Activating PKCα/ERK/NF-κB-Dependent MMP-2/MMP-9 Expressions

alpha-Tomatine, isolated from Lycopersicon esculentum Linn., is a naturally occurring glycoalkaloids in immature green tomatoes. Some reports demonstrated that alpha-tomatine had various anti-carcinogenic properties. First, the result demonstrated alpha-tomatine could inhibit TPA-induced the abilities of the adhesion, morphology/actin cytoskeleton arrangement, invasion, and migration by cell-matrix adhesion assay, immunofluorescence stain assay, Boyden chamber invasion assay, and wound-healing assay. Data also showed alpha-tomatine could inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and protein kinase C-alpha (PKC alpha) involved in the downregulation of the enzyme activities and messenger RNA levels of matrix metalloproteinase-2/9 (MMP-2/MMP-9) induced by TPA. Next, alpha-tomatine also strongly inhibited TPA-induced the activation of nuclear factor kappa B (NF-kappa B) and phospho-inhibitor of kappa B alpha (phospho-I kappa B alpha). In addition, TPA-induced translocation of PKC-alpha from cytosol to membranes, and suppression of TPA elicited the expression of PKC-alpha by adding the PKC-alpha inhibitors, GF-109203X and Go-6983. The treatment of specific inhibitor for ERK (U0126) to MCF-7 cells could inhibit TPA-induced MMP-2/MMP-9 and phospho-ERK along with an inhibition on cell invasion and migration. Application of alpha-tomatine to prevent the invasion/migration of MCF-7 cells through blocking PKC alpha/ERK/NF-kappa B activation is first demonstrated herein.