Abstract B68: EGCG and theaflavin are direct inhibitors of the oncogenic lipid kinase, sphingosine kinase 1

Epigallocatechin-3-gallate (EGCG) and theaflavin are polyphenols from green and black tea, respectively, that have been shown to have anti-cancer/anti-inflammatory effects through their antioxidant properties. Recent studies indicate that these tea polyphenols may also target the sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P) signaling pathway. Therefore we examined whether these tea polyphenols can directly inhibit SphK1 catalytic activity. To accomplish this, we performed in vitro SphK activity assays to determine the kinetics properties of EGCG and theaflavin toward SphK1. These analyses indicate that EGCG, and its related tea polyphenols theaflavin, GCG and catechin all directly inhibit SphK1 catalytic activity. Further kinetic analysis indicates that EGCG is a non-competitive inhibitor of SphK1 (K_i = 450-500 nM). These data are the first demonstration of a direct inhibitory effect of tea polyphenols on SphK1 catalytic activity. Importantly, given the oncogenic role of SphK1, they suggest that SphK1 is a target of the anti-cancer/anti-inflammatory actions of the tea polyphenols such as EGCG and theaflavin. They further suggest that inhibiting SphK1 activity, using tea polyphenols, can be an effective chemopreventative strategy and that the structures of these polyphenols could serve as novel molecular scaffolds for the development of SphK inhibitors.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):B68.