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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2013

Contributo in rivista

Tipo: Articolo in rivista

Titolo: RedOx Status, Proteasome and APEH: Insights into Anticancer Mechanisms of t10,c12-Conjugated Linoleic Acid Isomer on A375 Melanoma Cells

Anno di pubblicazione: 2013

Autori: Bergamo, Paolo; Cocca, Ennio; Palumbo, Rosanna; Gogliettino, Marta; Rossi, Mose; Palmieri, Gianna

Affiliazioni autori: ISA, IBP, IBB- CNR

Autori CNR:


Lingua: inglese

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.

Pagine da: e80900


PloS one Public Library of Science
Paese di pubblicazione: Stati Uniti d'America
Lingua: inglese
ISSN: 1932-6203

Numero volume: 8

Numero fascicolo: 11

DOI: 10.1371/journal.pone.0080900

Referee: Sì: Internazionale

Indicizzato da: PubMed [24260504]

Parole chiave:

  • Proteasome
  • antioxidant
  • apoptosi
  • oxidative stress

Strutture CNR:


Allegati: RedOx Status, Proteasome and APEH: Insights into Anticancer Mechanisms of t10,c12-Conjugated Linoleic Acid Isomer on A375 Melanoma Cells (application/pdf)

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