APEH Inhibition Affects Osteosarcoma Cell Viability via Downregulation of the Proteasome
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APEH Inhibition Affects Osteosarcoma Cell Viability via Downregulation of the Proteasome (56 visite)

Palumbo R, Gogliettino M, Cocca E, Iannitti R, Sandomenico A, Ruvo M, Balestrieri M, Rossi M, Palmieri G

Int J Mol Sci (ISSN: 1422-0067electronic, 1422-0067linking, 1661-6596), 2016 Sep 23; 17(10): N/D-N/D.

Tipo di articolo: Journal Article,

Impact factor: 3.226

Impact factor a 5 anni: 3.482


Parole chiave: Acylpeptide Hydrolase (apeh), Anti-Tumoral Target, Osteosarcoma Cell Lines, Peptide Inhibitor, Proteasome,

Url: Non disponibile.

The proteasome is a multienzymatic complex that controls the half-life of the majority of intracellular proteins, including those involved in apoptosis and cell-cycle progression. Recently, proteasome inhibition has been shown to be an effective anticancer strategy, although its downregulation is often accompanied by severe undesired side effects. We previously reported that the inhibition of acylpeptide hydrolase (APEH) by the peptide SsCEI 4 can significantly affect the proteasome activity in A375 melanoma or Caco-2 adenocarcinoma cell lines, thus shedding new light on therapeutic strategies based on downstream regulation of proteasome functions. In this work, we investigated the functional correlation between APEH and proteasome in a panel of cancer cell lines, and evaluated the cell proliferation upon SsCEI 4-treatments. Results revealed that SsCEI 4 triggered a proliferative arrest specifically in osteosarcoma U2OS cells via downregulation of the APEH-proteasome system, with the accumulation of the typical hallmarks of proteasome: NF-kappaB, p21(Waf1), and polyubiquitinylated proteins. We found that the SsCEI 4 anti-proliferative effect involved a senescence-like growth arrest without noticeable cytotoxicity. These findings represent an important step toward understanding the mechanism(s) underlying the APEH-mediated downregulation of proteasome in order to design new molecules able to efficiently regulate the proteasome system for alternative therapeutic strategies.
*** IBB - CNR ***

Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. rosanna.palumbo@cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. marta.gogliettino@ibbr.cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. ennio.cocca@ibbr.cnr.it., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. robertaiannitti@gmail.com., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. annamaria.sandomenico@gmail.com., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. menotti.ruvo@unina.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. marco.balestrieri@ibbr.cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. mose.rossi@ibbr.cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. gianna.palmieri@ibbr.cnr.it.,
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13 Records (12 escludendo Abstract e Conferenze).
Impact factor totale: 66.298 (62.764 escludendo Abstract e Conferenze).
Impact factor a 5 anni totale: 67.228 (63.213 escludendo Abstract e Conferenze).

Interrogazione bibliografica effettuata: (([btitle] "Acylpeptide Hydrolase (apeh)" OR [btitle] "Anti-Tumoral Target" OR [btitle] "Osteosarcoma Cell Lines" OR [btitle] "Peptide Inhibitor" OR [btitle] "Proteasome") AND NOT [id] = 53318)







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