Polyphenol inhibition of nucleoside diphosphate kinase-B activity and cancer metastasis

Abstract

Aggressive human tumor cells from disparate tissues were found to secrete nucleoside diphosphate kinase-B (NDPK-B) as a phosphoprotein into the extracellular environment. The secreted enzyme was capable of trasphosphorylation activity in the absence of a phosphoryl donor, thereby producing elevated level of extracellular ATP that plays a significant role in angiogenesis required for the growth of cancer cells and cancer metastasis. A series of structurally related non-nucleotide anticancer compounds such as ellagic acid (EA), epigallocatechin gallate (EGCG), and epicatechin gallate (ECG) were found to inhibit the activity of secreted nucleoside diphosphate kinase-B as well as angiogenesis. The nucleoside diphosphate kinase-B inhibition data disclosed herein can be used in predicative models to design novel inhibitors of nucleoside diphosphate kinase-B activity.

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