Inhibition of the interactions between metastatic human breast cancer cells and platelets by β-nitrostyrene derivatives.

Abstract

The interactions between cancer cells and platelets have been recognized to play an important role in cancer progress as well as metastasis, and interference with cancer-platelet interactions is an attractive strategy for cancer therapy. In the present study, two β-nitrostyrene derivatives: 3, 4-methylene-dioxy-β-nitrostyrene (MNS) and 4-O-benzoyl-3-methoxyl-β-nitrostyrene (BMNS) have been tested for their inhibitory effect on platelet activation caused by metastatic human breast cancer MDA-MB-231 and Hs578T cells. Washed human platelets were co-incubated with breast cancer cells, and platelet aggregation was determined turbidimetrically. Platelet adhesion to cancer cells and P-selectin expression were measured by flow cytometry. Platelet-derived growth factor (PDGF) released from cancer cell-stimulated platelets was determined by enzyme-linked immunosorbent assay (ELISA). MNS and BMNS prevented cancer cell-induced platelet aggregation, P-selectin expression, and PDGF secretion. Moreover, the β-nitrostyrenes reduced platelet adhesion to cancer cells, suggesting the initial cancer-platelet interactions are inhibited. In contrast to current antiplatelet strategies, the glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist RGDS peptide only prevented cancer cells-induced platelet aggregation, but not platelet adhesion and secretion; whereas the cyclooxygenase inhibitor aspirin and the adenosine diphosphate (ADP) scavenger apyrase affected neither platelet aggregation nor platelet secretion. The inhibitory effects of the β-nitrostyrene derivatives on cancer-platelet interactions may offer a potential approach for repressing cancer metastasis.