Trans-resveratrol, its dimer
epsilon-viniferin and two preparations of
vineatrol (a grape-derived
polyphenol fraction isolated from vine-shots extracts) were compared for their effects on the proliferation and survival of normal and leukemic human lymphocytes. The two different batches of
vineatrol (
vineatrol 10 and 25%) was obtained by HPLC fractionation and contained 10 and 25%
trans-resveratrol, respectively. The different
polyphenols were added to cultures of leukemic cells from chronic B cell
malignancies (
B-cell chronic lymphocytic leukemia, B-CLL or
hairy cell leukemia, HCL) or normal peripheral blood-derived mononuclear cells (PBMC) as a control. The different
polyphenols displayed anti-proliferative effect on the leukemic cells, as estimated by the observed inhibition of tritiated
thymidine uptake and the reduction of cell recovery.
Vineatrol 10% was the most potent whereas
vineatrol 25% and
resveratrol displayed comparable activity,
epsilon-viniferin only exhibiting slight effets. The same order of potency was observed for their capacity to induce apoptosis in leukemic B cells. In contrast, the survival of normal peripheral blood mononuclear cells (PBMC) was little affected in the presence of these polyphenolic compounds and higher concentrations were required in order to elicit cell death.
Polyphenol-driven apoptosis in chronic leukemic B cells was shown to correlate with an activation of
caspase 3, a drop in the mitochondrial transmembrane potential, a reduction in the expression of the
anti-apoptotic protein bcl-2, as well as a reduction in the expression of the
inducible nitric oxide synthase (iNOS). Our data therefore indicate that vine-shoots may be a convenient and natural source of material for the purification of
resveratrol and other polyphenolic compounds of putative therapeutic interest.