Please use this identifier to cite or link to this item: http://hdl.handle.net/2067/34190
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dc.contributor.authorGilardini Montani Msit
dc.contributor.authorGranato, M.it
dc.contributor.authorSantoni, C.it
dc.contributor.authorDel Porto, P.it
dc.contributor.authorMerendino, Nicolo'it
dc.contributor.authorDorazi, G.it
dc.contributor.authorFaggioni, A.it
dc.contributor.authorCirone, M.it
dc.date.accessioned2020-10-20T22:52:47Z-
dc.date.available2020-10-20T22:52:47Z-
dc.date.issued2017it
dc.identifier.issn1570-5870it
dc.identifier.urihttp://hdl.handle.net/2067/34190-
dc.description.abstractHistone deacetylase inhibitors (HDACis) are antineoplastic agents that affect cell growth, differentiation and invasion in a variety of different cancer types, although the underlying mechanisms have not been completely clarified yet. In this study, we compared the effects of two HDACis, namely Trichostatin A (TSA) and Valproic Acid (VPA) in the induction of both cell death and autophagy in the pancreatic cancer cell lines PaCa44 and Panc1. These cells are characterized by a high metastatic capacity and display k-RAS/p53 double mutation. We found that both HDACis reduced cell survival and induced pancreatic cancer cells apoptosis by triggering mitochondrial membrane depolarization, cytochrome C release and caspase 3 activation, although VPA was more effective than TSA, especially in Panc1. Among the underlying molecular mechanism/s leading to the HDACis-mediated cytotoxic effect, we found that ERK1/2 was de-phosphorylated and c-Myc and mutant p53 protein levels were reduced by VPA and to a lesser extent by TSA. Up-regulation of p21 and Puma was also observed, suggesting a possible wild-type p53 re-activation, concomitantly with mutant p53 degradation. In addition, in both cell lines VPA increased the pro-apoptotic Bim, reduced the anti-apoptotic Mcl-1, induced ROS production and autophagy while TSA was able to mediate these effects only in PaCA44 cells. These results suggest that VPA, that specifically inhibits class I HDAC, may have a stronger and broader cytotoxic effect in comparison with TSA against pancreatic cancer and could represent a better choice in pancreatic anticancer therapy, alone or in combination with other drugs.it
dc.format.mediumSTAMPAit
dc.rightsAttribution-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-sa/4.0/*
dc.titleHistone deacetylase inhibitors VPA and TSA induce apoptosis and autophagy in pancreatic cancer cellsit
dc.typearticleen
dc.identifier.doi10.1007/s13402-017-0314-zit
dc.identifier.scopus2-s2-85011632951it
dc.identifier.isi398457200006it
dc.relation.issn22113428en
dc.relation.journalCELLULAR ONCOLOGYit
dc.relation.firstpage167it
dc.relation.lastpage180it
dc.relation.numberofpages14it
dc.relation.conferencenameCELLULAIR ONCOLOGYen
dc.relation.volume40it
dc.relation.issue40it
dc.description.internationalnoit
dc.type.refereeREF_1it
dc.type.miur262en
item.fulltextWith Fulltext-
item.openairetypearticle-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.journal.journalissn1570-5870-
crisitem.journal.anceE185520-
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