Comparative antiproliferative and apoptotic effects of resveratrol, epsilon-viniferin and vine-shots derived polyphenols (vineatrols) on chronic B lymphocytic leukemia cells and normal human lymphocytes.
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.
Billard
Christian
C
U365 INSERM, Institut Curie, 26 rue d'Ulm, 75248, Paris Cedex 05, France.
Izard
Jean-Claude
JC
Roman
Viviana
V
Kern
Catherine
C
Mathiot
Claire
C
Mentz
Franck
F
Kolb
Jean-Pierre
JP
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005419:Flavonoids; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000648:ultrastructure; D019001:Nitric Oxide Synthase / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D027843:Vitis / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D001572:Benzofurans; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D011108:Polymers; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; C091891:epsilon-viniferin; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077185:Resveratrol