title: Resveratrol diminishes platelet aggregation and increases susceptibility of K562 tumor cells to natural killer cells.
abstract: Platelet aggregation around migrating cancer cells protects them against the activity of natural killer cells (NKCs). The inability of immune system to response results in the progression of malignant diseases. This study was designed to evaluate the effects of resveratrol (3, 4', 5-trihydroxystilbene) on platelet aggregation and NKCs activity. Experiments were designed to evaluate the platelet aggregation, production of thromboxane B2 (TXB2), estimation of expression of the platelet receptor GpIIb/IIIa (major biological markers for platelet aggregation) and functional activity of the NKCs against the K562 cancer cell line after incubation with various concentrations of reveratrol. Resveratrol at a concentration of 3 x 10(-3)M completely inhibited platelet aggregation (p < 0.05), decreased TXB2 levels (p < 0.05) and inhibited the expression of receptor GpIIb/IIIa in non-stimulated platelets (p < 0.05). At the same concentration, it increased the NKCs cytotoxic activity at an average rate of 319 +/- 34, 450 +/- 34 and 62 +/- 2.4% (p < 0.05) in the NKC/targets cells ratios of 12.5:1, 25:1 and 50:1, respectively. Thus, resveratrol not only completely inhibited platelet aggregation and reduced TXB2 levels and expression of receptor GpIIb/IIIa, but also increased the cytotoxic activity of NKCs in vitro and thus increased the susceptibility of tumor cells to NKCs. Thus, resveratrol can be used as an additional supplement to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes. Further clinical investigation in vivo could lead to specific concentrations that may maximize the beneficial effect of resveratrol.
authors.affiliation: Laboratory of Physiology, Faculty of Medicine, University of Ioannina, Ioannina 45110, Greece. johntolio@hotmail.com
authors.forename: Ioannis K
authors.initials: IK
authors.lastname: Toliopoulos
authors.forename: Yannis V
authors.initials: YV
authors.lastname: Simos
authors.forename: Stergios
authors.initials: S
authors.lastname: Oikonomidis
authors.forename: Spyros C
authors.initials: SC
authors.lastname: Karkabounas
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000276:immunology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010975:Platelet Aggregation Inhibitors; D013267:Stilbenes; D000077185:Resveratrol