title: 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.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan.
authors.forename: Min-Der
authors.initials: MD
authors.lastname: Shi
authors.forename: Yuan-Wei
authors.initials: YW
authors.lastname: Shih
authors.forename: Ya-Shan
authors.initials: YS
authors.lastname: Lee
authors.forename: Yueh-Feng
authors.initials: YF
authors.lastname: Cheng
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Tsai
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D014053:Tomatine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015533:Transcriptional Activation
chemical_list: C554292:12-O-tetradecanoylphorbol-1,3-acetate; D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; C484751:alpha-tomatine; D014053:Tomatine; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate