Document Detail


Resveratrol-mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation.
MedLine Citation:
PMID:  22833338     Owner:  NLM     Status:  MEDLINE    
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 hr 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.
Authors:
Raffaele Frazzi; Riccardo Valli; Ione Tamagnini; Bruno Casali; Norbert Latruffe; Francesco Merli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-07
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  132     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-05-22     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1013-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 UICC.
Affiliation:
Hematology Unit, Oncology Department, IRCCS - Arcispedale S. Maria Nuova, Reggio Emilia, Italy. raffaele.frazzi@asmn.re.it
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MeSH Terms
Descriptor/Qualifier:
Acetylation / drug effects
Apoptosis / drug effects*,  genetics
B-Lymphocytes / drug effects,  metabolism
Caspase 3 / genetics,  metabolism
Cell Growth Processes / drug effects
Cell Line, Tumor
Dose-Response Relationship, Drug
Forkhead Transcription Factors / metabolism*
Germinal Center / drug effects,  metabolism
Hodgkin Disease / drug therapy*,  genetics,  metabolism*,  pathology
Humans
Lymph Nodes / drug effects,  metabolism
S Phase / drug effects,  genetics
Sirtuin 1 / antagonists & inhibitors*,  genetics,  metabolism
Stilbenes / pharmacology*
Tumor Suppressor Protein p53 / genetics,  metabolism
bcl-2-Associated X Protein / genetics,  metabolism
Chemical
Reg. No./Substance:
0/BAX protein, human; 0/FOXO3 protein, human; 0/Forkhead Transcription Factors; 0/Stilbenes; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; EC 3.4.22.-/Caspase 3; EC 3.5.1.-/SIRT1 protein, human; EC 3.5.1.-/Sirtuin 1; Q369O8926L/resveratrol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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