@prefix pubblicazioni: . @prefix unitaDiPersonaleInterno: . @prefix prodotto: . unitaDiPersonaleInterno:MATRICOLA29566 pubblicazioni:autoreCNRDi prodotto:ID12109 . @prefix prodottidellaricerca: . @prefix istituto: . istituto:CDS014 prodottidellaricerca:prodotto prodotto:ID12109 . unitaDiPersonaleInterno:MATRICOLA5615 pubblicazioni:autoreCNRDi prodotto:ID12109 . unitaDiPersonaleInterno:MATRICOLA8163 pubblicazioni:autoreCNRDi prodotto:ID12109 . @prefix modulo: . modulo:ID2565 prodottidellaricerca:prodotto prodotto:ID12109 . @prefix rdf: . @prefix retescientifica: . prodotto:ID12109 rdf:type retescientifica:ProdottoDellaRicerca , prodotto:TIPO1101 . @prefix rdfs: . prodotto:ID12109 rdfs:label "Potentiation of the antitumor effects of both selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors in human hepatic cancer cells by inhibition of the MEK/ERK pathway (Articolo in rivista)"@en . @prefix xsd: . prodotto:ID12109 pubblicazioni:anno "2007-01-01T00:00:00+01:00"^^xsd:gYear . @prefix skos: . prodotto:ID12109 skos:altLabel "
Cusimano A, Foder\u00E0 D, D\u0092Alessandro N, Lampiasi N, Azzolina A, Montalto G, Cervello M (2007)
Potentiation of the antitumor effects of both selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors in human hepatic cancer cells by inhibition of the MEK/ERK pathway
in Cancer biology & therapy (Print)
"^^rdf:HTML ; pubblicazioni:autori "Cusimano A, Foder\u00E0 D, D\u0092Alessandro N, Lampiasi N, Azzolina A, Montalto G, Cervello M"^^xsd:string ; pubblicazioni:paginaInizio "1461"^^xsd:string ; pubblicazioni:paginaFine "1468"^^xsd:string ; pubblicazioni:numeroVolume "6"^^xsd:string . @prefix ns11: . prodotto:ID12109 pubblicazioni:rivista ns11:ID65907 ; skos:note "ISI Web of Science (WOS)"^^xsd:string ; pubblicazioni:affiliazioni "Istituto di Biomedicina e Immunologia Molecolare \\\"Alberto Monroy\\\"; Consiglio Nazionale delle Ricerche; Palermo, Italy\nDipartimento di Medicina Clinica e Patologie Emergenti; Universit\u00E0 di Palermo; Palermo, Italy\nDipartimento di Scienze Farmacologiche; Universit\u00E0 di Palermo; Palermo, Italy"^^xsd:string ; pubblicazioni:titolo "Potentiation of the antitumor effects of both selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors in human hepatic cancer cells by inhibition of the MEK/ERK pathway"^^xsd:string ; prodottidellaricerca:abstract "The molecular mechanisms behind the anti-neoplastic effects of non-steroidal antiinflammatory\ndrugs (NSAIDs) are not completely understood and cannot be explained\nby the inhibition of the cyclooxygenase (COX) enzymes COX-1 and COX-2 alone. We\npreviously reported that both the selective COX-1 inhibitor SC-560 and the selective\nCOX-2 inhibitor CAY10404 exhibit antitumor effects in human hepatoma cells. NSAID\ninhibitors have many COX-independent actions and, among others, the mitogen-activated\nprotein kinase (MAPK) pathways are targets for NSAIDs. Here, we examined the role of\nMEK/ERK1/2 signaling in the anti-neoplastic effects of both selective COX-1 and COX-2\ninhibitors in two human hepatoma cell lines. Treatment of hepatoma cells with the selective\nCOX-1 inhibitor SC-560, as well as with the selective COX-2 inhibitor CAY10404,\nwas associated with activation of ERK1/2 in a time- and dose-dependent manner.\nTreatment with COX-1 and COX-2 inhibitors in the presence of the selective MEK1/2\ninhibitor U0126 effectively suppressed ERK1/2 activation and combinations of either\nSC-560 or CAY10404 with U0126 resulted in synergistic effects on cell growth inhibition\nand induction of apoptosis. In HuH-6 hepatoma cells the combination-induced apoptosis\nwas associated with caspase-9 and -3 activation, PARP cleavage, release of cytochrome\nc from the mitochondria into the cytosol and downregulation of survivin and b-catenin\nlevels. In conclusion, our study showed that growth inhibitory concentrations of selective\nCOX-1 and COX-2 inhibitors increased ERK1/2 phosphorylation in hepatoma cells, and\nthat inhibition of the MEK/ERK signaling pathway potentiates the antitumor activity of\nboth types of inhibitors. Therefore, our results provide preclinical support for a combined\nchemotherapeutic approach with selective NSAIDs and MEK inhibitors for the treatment\nof hepatocellular carcinoma."@en ; prodottidellaricerca:prodottoDi istituto:CDS014 , modulo:ID2565 ; pubblicazioni:autoreCNR unitaDiPersonaleInterno:MATRICOLA8163 , unitaDiPersonaleInterno:MATRICOLA29566 , unitaDiPersonaleInterno:MATRICOLA5615 . ns11:ID65907 pubblicazioni:rivistaDi prodotto:ID12109 .