Please use this identifier to cite or link to this item:
http://hdl.handle.net/2067/34190
DC Field | Value | Language |
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dc.contributor.author | Gilardini Montani Ms | it |
dc.contributor.author | Granato, M. | it |
dc.contributor.author | Santoni, C. | it |
dc.contributor.author | Del Porto, P. | it |
dc.contributor.author | Merendino, Nicolo' | it |
dc.contributor.author | Dorazi, G. | it |
dc.contributor.author | Faggioni, A. | it |
dc.contributor.author | Cirone, M. | it |
dc.date.accessioned | 2020-10-20T22:52:47Z | - |
dc.date.available | 2020-10-20T22:52:47Z | - |
dc.date.issued | 2017 | it |
dc.identifier.issn | 1570-5870 | it |
dc.identifier.uri | http://hdl.handle.net/2067/34190 | - |
dc.description.abstract | Histone 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.medium | STAMPA | it |
dc.rights | Attribution-ShareAlike 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | * |
dc.title | Histone deacetylase inhibitors VPA and TSA induce apoptosis and autophagy in pancreatic cancer cells | it |
dc.type | article | en |
dc.identifier.doi | 10.1007/s13402-017-0314-z | it |
dc.identifier.scopus | 2-s2-85011632951 | it |
dc.identifier.isi | 398457200006 | it |
dc.relation.issn | 22113428 | en |
dc.relation.journal | CELLULAR ONCOLOGY | it |
dc.relation.firstpage | 167 | it |
dc.relation.lastpage | 180 | it |
dc.relation.numberofpages | 14 | it |
dc.relation.conferencename | CELLULAIR ONCOLOGY | en |
dc.relation.volume | 40 | it |
dc.relation.issue | 40 | it |
dc.description.international | no | it |
dc.type.referee | REF_1 | it |
dc.type.miur | 262 | en |
item.fulltext | With Fulltext | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.journal.journalissn | 1570-5870 | - |
crisitem.journal.ance | E185520 | - |
Appears in Collections: | A1. Articolo in rivista |
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BBAMCR-S-16-00509 (1).pdf | 865.74 kB | Adobe PDF | View/Open |
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