Sulfated Polysaccharides from Macroalgae Are Potent Dual Inhibitors of Human ATP-Hydrolyzing Ectonucleotidases NPP1 and CD39

Extracellular ATP mediates proinflammatory and antiproliferative effects via activation of P2 nucleotide receptors. In contrast, its metabolite, the nucleoside adenosine, is strongly immunosuppressive enhances tumor proliferation metastasis. The conversion to adenosine catalyzed by ectonucleotidases, which are expressed on immune cells typically upregulated cells. present study, we identified sulfopolysaccharides from brown red sea algae act as potent dual inhibitors main ATP-hydrolyzing ectoenzymes, ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) ecto-nucleoside triphosphate diphosphohydrolase-1 (NTPDase1, CD39), showing nano- picomolar potency displaying a non-competitive mechanism inhibition. We showed that one tested representative example reduced formation at surface human glioblastoma cell line U87 in concentration-dependent manner. These natural products represent most extracellular hydrolysis known date have potential novel therapeutics for immunotherapy cancer.