NAMI-A inhibits the PMA-induced ODC gene expression in ECV304 cells: involvement of PKC/Raf/Mek/ERK signalling pathway.
Imidazolium trans-imidazole dimethyl sulfoxide tetrachlororuthenate (NAMI-A) is a new compound active against lung metastasis of solid metastasizing tumours. While its in vivo effect has been studied, the molecular insights that underlie its action are largely unknown. Among the possible pathways responsible for malignant transformation, PKC arose as one of the most promising targets for new antineoplastic drugs. We demonstrated the capability of NAMI-A of inhibiting PMA induced-PKC activity in ECV304 in a dose-dependent fashion. Furthermore, NAMI-A through modulation of PKC activity has been proved capable of reducing the phorbol ester induced expression of ornithine decarboxilase (ODC) gene and to abrogate the activation of the Raf/MEK/ERK pathway. Taken together these results suggest that many of the in vivo outcomes of NAMI-A treatment may be the result of a direct action on PKC.
Debidda
Marcella
M
Department of Biomedical Sciences, Division of Biochemistry, Laboratory of Cardiovascular Research, National Institute of Biostructures and Biosystems, University of Sassari, I-07100 Sassari, Italy.
Sanna
Bastiano
B
Cossu
Annalisa
A
Posadino
Anna M
AM
Tadolini
B
B
Ventura
C
C
Pintus
G
G
D015153:Blotting, Western; D002461:Cell Line, Transformed / Q000201:enzymology*; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017975:Ruthenium Compounds; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide