RedOx Status, Proteasome and APEH: Insights into Anticancer Mechanisms of t10,c12-Conjugated Linoleic Acid Isomer on A375 Melanoma Cells (Articolo in rivista)

Type
Label
  • RedOx Status, Proteasome and APEH: Insights into Anticancer Mechanisms of t10,c12-Conjugated Linoleic Acid Isomer on A375 Melanoma Cells (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1371/journal.pone.0080900 (literal)
Alternative label
  • Bergamo, Paolo; Cocca, Ennio; Palumbo, Rosanna; Gogliettino, Marta; Rossi, Mose; Palmieri, Gianna (2013)
    RedOx Status, Proteasome and APEH: Insights into Anticancer Mechanisms of t10,c12-Conjugated Linoleic Acid Isomer on A375 Melanoma Cells
    in PloS one
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Bergamo, Paolo; Cocca, Ennio; Palumbo, Rosanna; Gogliettino, Marta; Rossi, Mose; Palmieri, Gianna (literal)
Pagina inizio
  • e80900 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 8 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 11 (literal)
Note
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • ISA, IBP, IBB- CNR (literal)
Titolo
  • RedOx Status, Proteasome and APEH: Insights into Anticancer Mechanisms of t10,c12-Conjugated Linoleic Acid Isomer on A375 Melanoma Cells (literal)
Abstract
  • This study describes the investigation of the efficiency of conjugated linoleic acid (CLA) isomers in reducing cancer cells viability exploring the role of the oxidative stress and acylpeptide hydrolase (APEH)/proteasome mediated pathways on pro-apoptotic activity of the isomer trans10,cis12 (t10,c12)-CLA. The basal activity/expression levels of APEH and proteasome (beta-5 subunit) were preliminarily measured in eight cancer cell lines and the functional relationship between these enzymes was clearly demonstrated through their strong positive correlation. t10,c12-CLA efficiently inhibited the activity of APEH and proteasome isoforms in cell-free assays and the negative correlation between cell viability and caspase 3 activity confirmed the pro-apoptotic role of this isomer. Finally, modulatory effects of t10,c12-CLA on cellular redox status (intracellular glutathione, mRNA levels of antioxidant/detoxifying enzymes activated through NF-E2-related factor 2, Nrf2, pathway) and on APEH/beta-5 activity/expression levels, were investigated in A375 melanoma cells. Dose- and time-dependent variations of the considered parameters were established and the resulting pro-apoptotic effects were shown to be associated with an alteration of the redox status and a down-regulation of APEH/proteasome pathway. Therefore, our results support the idea that these events are involved in ROS-dependent apoptosis of t10,c12-CLA-treated A375 cells. The combined inhibition, triggered by t10,c12-CLA, via the modulation of APEH/proteasome and Nrf2 pathway for treating melanoma, is suggested as a subject for further in vivo studies. (literal)
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