Epigallocatechin-3-gallate shows anti-proliferative activity in HeLa cells targeting tubulin-microtubule equilibrium

In this study our main objective was to find out a novel target of the major bioactive green tea polyphenol, Epigallocatechin-3-gallate (EGCG), in cervical carcinoma HeLa cells. We found that EGCG showed antiproliferative activity against HeLa cells through depolymerization of cellular microtubule. EGCG also prevented the reformation of the cellular microtubule network distorted by cold treatment and inhibited polymerization of tubulin in cell-free system with IC50 of 39.6 +/- 0.63 mu M. Fluorescence spectroscopic analysis showed that EGCG prevented colchicine binding to tubulin and in silico study revealed that EGCG bound to the alpha-subunit of tubulin at the interphase of the alpha-and beta-heterodimers and very close to colchicine binding site. The binding is entropy driven (Delta S-0 was 18.75 +/- 1.48 cal K-1 mol(-1)) with Kd value of 3.50 +/- 0.40 mu M. This is a novel mechanism of antipriliferative activity of EGCG. (C) 2015 Elsevier Ireland Ltd. All rights reserved.