Inhibition of platelet aggregation and stimulation of natural killer cells functionality by administration of flavonoids

Platelets play an important role in homeostasis, inflammation and regulation of immune response. Natural Killer cells (NKC) on the other hand are the first line of defense of the immune system against viruses, bacteria and cancer cells. Platelets directly protect tumor cells from NK lysis. Thus, platelet aggregation around migrating cancer cells as well as the response of the immune system constitutes important mechanisms, which influence the progression of malignant diseases. The present study was designed to evaluate the possible effects of flavonoids (genistein, apigenin and quercetin) on the stimulation of the immune system and the inhibition of platelet aggregation. Two experimental protocols were used: a) ex vivo aggregation of human platelets, production of thromboxane A2 (TXA2) and estimation of the expression of the platelet membranic receptor GpIIb/IIIa, and b) functional activity of human NK lymphocytes against K562 target cells in vitro. All substances were found to induce a dose dependent inhibition of platelet aggregation and to reduce production of TXA2 in platelets. There was a decrease in the number of the GpIIb/IIIa receptors on the platelets surface membrane. Flow cytometry analysis revealed that all substances powerfully reinforce cytotoxic activity of NKC against K562 cells. These results show that flavonoids increase the susceptibility of tumor cells to NK cells by decreasing platelet aggregation and stimulating the NK lymphocyte activity.