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

• Published in: Cell biochemistry and biophysics 2013-05, Vol.66 (1), p.161-174
• Main Authors: Shi, Min-Der, Shih, Yuan-Wei, Lee, Ya-Shan, Cheng, Yueh-Feng, Tsai, Li-Yu
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - drug effects; Antineoplastic Agents, Phytogenic - pharmacology; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Biotechnology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Adhesion - drug effects; Cell Biology; Cell Movement; Cell Shape - drug effects; Cell Survival - drug effects; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Life Sciences; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; MCF-7 Cells; Neoplasm Invasiveness - pathology; NF-kappa B - metabolism; Original Paper; Pharmacology/Toxicology; Phosphorylation; Protein Kinase C-alpha - genetics; Protein Kinase C-alpha - metabolism; Tetradecanoylphorbol Acetate - analogs & derivatives; Tetradecanoylphorbol Acetate - pharmacology; Tomatine - analogs & derivatives; Tomatine - pharmacology; Transcriptional Activation
• ISSN: 1085-9195; 1559-0283
• DOI: 10.1007/s12013-012-9465-8

α-Tomatine, isolated from Lycopersicon esculentum Linn., is a naturally occurring glycoalkaloids in immature green tomatoes. Some reports demonstrated that α-tomatine had various anti-carcinogenic properties. First, the result demonstrated α-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 α-tomatine could inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and protein kinase C-α (PKCα) 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, α-tomatine also strongly inhibited TPA-induced the activation of nuclear factor kappa B (NF-κB) and phospho-inhibitor of kappa Bα (phospho-IκBα). In addition, TPA-induced translocation of PKC-α from cytosol to membranes, and suppression of TPA elicited the expression of PKC-α by adding the PKC-α inhibitors, GF-109203X and Gö-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 α-tomatine to prevent the invasion/migration of MCF-7 cells through blocking PKCα/ERK/NF-κB activation is first demonstrated herein.