Anticancer Effect of Epitheaflagallin 3‑<i>O</i>‑Gallate, a Very Minor Constituent of Black Tea Extract

Abstract

Epitheaflagallin (ETFG) and epitheaflagallin 3-O-gallate (ETFGg) are minor polyphenols found in black tea extract that can be enzymatically synthesized from epigallocatechin (EGC) and epigallocatechin 3-O-gallate (EGCg), respectively, in green tea extract via laccase oxidation in the presence of gallic acid. Both compounds exhibit versatile physiological functions in vivo and in vitro, including antioxidative activity, pancreatic lipase inhibition, glycosyltransferase inhibition, and inhibition of matrix metalloprotease (MMP)-1 and MMP-3 activity and synthesis. We recently succeeded in efficiently producing ETFGg from EGCg and gallic acid by using recombinant Hericium collaroides laccase (Lcc2) in a biphasic reaction system. Using this sample, we conducted an in silico survey and in vivo tests to investigate whether ETFGg can prevent cancer based on known data showing the cancer-prevention effects of EGCg, which is a major and active component in green tea extract. We conducted docking simulation studies of the inhibitory effects of ETFGg and related compounds toward MMP-2 and MMP-9, two antiapoptotic B-cell lymphoma (Bcl)-2-family proteins, and 67-kDa laminin receptor protein (67LR). The results suggested that ETFGg interacts more strongly with Bcl-2 family proteins and 67LR compared with EGCg. Data showing the effect of ETFGg on an in vivo mouse metastasis model indicated that ETFGg is a promising functional food ingredient with potential anticancer activities. Moreover, we investigated the antidiabetic effect of ETFGg in a type-2 diabetes model mouse (KK-Ay/TaJcl) but observed no significant blood glucose inhibitory effect