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

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. What's new? Resveratrol (RSV) is a plant polyphenol with promising anticancer features. In this study, the authors examined whether RSV could reduce proliferation of a Hodgkin‐lymphoma (HL) cell line. They found that exposure to RSV led to an almost 20‐fold increase in apoptosis and cell death, as well as reduced activity of sirtuin‐1 (SIRT1). In addition to supporting a therapeutic role for RSV, data from this study suggest that SIRT1 may play a role in malignant transformation, and might have potential as a therapeutic target.