Epigallocatechin-3-gallate shows anti-proliferative activity in HeLa cells targeting tubulin-microtubule equilibrium. (5th December 2015)

• Record Type: Journal Article
• Authors: Chakrabarty, Subhendu; Ganguli, Arnab; Das, Amlan; Nag, Debasish; Chakrabarti, Gopal
• Is Part Of: Chemico-biological interactions. Volume 242(2015)
• Page Start: 380
• Page End: 389
• Publication Date: 2015-12-05
• Subjects: EGCG -- Tubulin-microtubule -- Cervical cancer -- Immunofluorescence -- Spectroscopy; DMEM Dulbecco's minimal essential media -- FBS fetal bovine serum -- DAPI 4′, 6-diamidino-2-phenylindole -- GTP guanosine-5′-triphosphate -- PIPES piperazine-1, 4-bis(2-ethanesulfonic acid) -- PBS phosphate buffered saline; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2015.11.004
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: 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 μM. Fluorescence spectroscopic analysis showed that EGCG prevented colchicine binding to tubulin and in silico study revealed that EGCG bound to the α-subunit of tubulin at the interphase of the α-and β-heterodimers and very close to colchicine binding site. The binding is entropy driven (ΔS 0 was 18.75 ± 1.48 cal K −1 mol −1 ) with Kd value of 3.50 ± 0.40 μM. This is a novel mechanism of antipriliferative activity of EGCG. Graphical abstract: Highlights: EGCG shows antiproliferative activity in HeLa cells with an IC50 value of 54 μM. EGCG depolymerizes cellular microtubules and arrest cell cycle at G2 /M phase. Polymerization of tissue purified tubulin is prevented by EGCG. EGCG binds on tubulin near colchicine binding site. EGCG-tubulin binding is entropy driven reaction with Kd value around 3.5 μM.