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

Abstract

AIMS:

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.

MAIN METHODS:

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).

KEY FINDINGS:

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.

SIGNIFICANCE:

The inhibitory effects of the β-nitrostyrene derivatives on cancer-platelet interactions may offer a potential approach for repressing cancer metastasis.

• Authors: Chien-Kei Wei, Fang-Rong Chang, Pei-Wen Hsieh, Chin-Chung Wu
• Journal: Life sciences (Life Sci) Vol. 143 Pg. 147-55 (Dec 15 2015) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 26546721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Platelet Aggregation Inhibitors
• Styrenes
• beta-nitrostyrene

Topics

• Blood Platelets (drug effects, metabolism)
• Breast Neoplasms (drug therapy, metabolism)
• Cell Adhesion (drug effects, physiology)
• Cell Survival (drug effects, physiology)
• Dose-Response Relationship, Drug
• Female
• Humans
• MCF-7 Cells
• Platelet Aggregation (drug effects, physiology)
• Platelet Aggregation Inhibitors (chemistry, pharmacology)
• Styrenes (chemistry, pharmacology, therapeutic use)