Format

Send to

Choose Destination
Int J Cancer. 2013 Mar 1;132(5):1013-21. doi: 10.1002/ijc.27748. Epub 2012 Aug 7.

Resveratrol-mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation.

Author information

1
Hematology Unit, Oncology Department, IRCCS - Arcispedale S. Maria Nuova, Reggio Emilia, Italy. raffaele.frazzi@asmn.re.it

Abstract

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.

PMID:
22833338
DOI:
10.1002/ijc.27748
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center