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.

Abstract

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.

• Authors: Min-Der Shi, Yuan-Wei Shih, Ya-Shan Lee, Yueh-Feng Cheng, Li-Yu Tsai
• Journal: Cell biochemistry and biophysics (Cell Biochem Biophys) Vol. 66 Issue 1 Pg. 161-74 (May 2013) ISSN: 1559-0283 [Electronic] United States
• PMID: 23114726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 12-O-tetradecanoylphorbol-1,3-acetate
• Antineoplastic Agents, Phytogenic
• NF-kappa B
• alpha-tomatine
• Tomatine
• PRKCA protein, human
• Protein Kinase C-alpha
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9
• Tetradecanoylphorbol Acetate

Topics

• Actin Cytoskeleton (drug effects)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Breast Neoplasms (metabolism, pathology)
• Cell Adhesion (drug effects)
• Cell Movement
• Cell Shape (drug effects)
• Cell Survival (drug effects)
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• MCF-7 Cells
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• NF-kappa B (metabolism)
• Neoplasm Invasiveness (pathology)
• Phosphorylation
• Protein Kinase C-alpha (genetics, metabolism)
• Tetradecanoylphorbol Acetate (analogs & derivatives, pharmacology)
• Tomatine (analogs & derivatives, pharmacology)
• Transcriptional Activation