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Resveratrol-mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation.
MedLine Citation:
PMID:  22833338     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Resveratrol (RSV), a plant-derived stilbene, induces cell death in Hodgkin lymphoma (HL)-derived L-428 cells in a dose-dependent manner (IC50=27 μM, trypan blue exclusion assay). At a lower range (25 μM), RSV treatment for 48 hours causes arrest in the S-phase of the cell cycle, while at a higher concentration range (50 μM), apoptosis can be detected, with activation of caspase-3. The histone/protein deacetylase SIRT1 has been described as a putative target of RSV action in other model systems, even though its role in cancer cells is still controversial. Here we show that RSV, at both concentration ranges, leads to a marked increase in p53, while a decrease of SIRT1 expression level, as well as enzyme activity, only occurred at the higher concentration range. Concomitantly, however, treatments at both concentration ranges resulted in a marked increase in K373-acetylated p53 and lysine-acetylated FOXO3a. Immunohistochemical stainings of human lymph nodes show a preferential distribution of SIRT1 in the germinal center of the follicles while the mantle zone shows nearly no staining to few positive cells. The classical HL-affected lymph nodes show a strong positivity of the diagnostic Hodgkin Reed-Sternberg cells. Notably, both the HL-derived cell lines and the Hodgkin Reed-Sternberg cells of the affected lymph nodes derive from germinal center-derived B cells. The study of SIRT1 distribution and expression on a larger number of biopsies might disclose a novel role for this histone/protein deacetylase as therapeutic target. © 2012 Wiley Periodicals, Inc.
Authors:
Raffaele Frazzi; Riccardo Valli; Ione Tamagnini; Bruno Casali; Norbert Latruffe; Francesco Merli
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-26
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 UICC.
Affiliation:
Hematology Unit, Oncology Department, IRCCS - Arcispedale S.Maria Nuova, Reggio Emilia, Italy; Laboratory of Molecular Biology, Oncology Department, IRCCS - Arcispedale S.Maria Nuova, Reggio Emilia, Italy. raffaele.frazzi@asmn.re.it.
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