The anticancer agent ellipticine binds to glycosaminoglycans at mildly acidic pH characteristic of the extracellular matrix of tumor tissues

Abstract

In the first instance, this communication demonstrates the glycosaminoglycan (GAG) binding of the anticancer plant alkaloid ellipticine. Its association to heparin and heparan sulfate induces UV hypochromism and a biphasic circular dichroism (CD) signature originating from alkaloid–alkaloid chiral intermolecular exciton coupling. As the pH dependence of the CD signals showed, only the protonated form of ellipticine is capable to bind to the GAG chains. The binding is most prominent in the pH range of 6–7 which corresponds to the mildly acidic extracellular milieu of solid tumors and inflamed tissues. This implies that besides DNA intercalation, ellipticine may exert additional biological effects by targeting selectively the dynamic GAG–protein interaction network of the acidic tumor microenvironment that is crucial in the maintenance of the malignant phenotype.