title: Epigallocatechin-3-gallate shows anti-proliferative activity in HeLa cells targeting tubulin-microtubule equilibrium.
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.
authors.affiliation: Department of Biotechnology and Dr. B. C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB 700019, India.
authors.forename: Subhendu
authors.initials: S
authors.lastname: Chakrabarty
authors.affiliation: Department of Biotechnology and Dr. B. C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB 700019, India.
authors.forename: Arnab
authors.initials: A
authors.lastname: Ganguli
authors.affiliation: Department of Biotechnology and Dr. B. C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB 700019, India.
authors.forename: Amlan
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of Biotechnology and Dr. B. C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB 700019, India.
authors.forename: Debasish
authors.initials: D
authors.lastname: Nag
authors.affiliation: Department of Biotechnology and Dr. B. C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB 700019, India. Electronic address: gcbcg@caluniv.ac.in.
authors.forename: Gopal
authors.initials: G
authors.lastname: Chakrabarti
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D058105:Polymerization / Q000187:drug effects; D011487:Protein Conformation; D013816:Thermodynamics; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D002392:Catechin; C045651:epigallocatechin gallate; D003078:Colchicine
keywords: Cervical cancer; EGCG; Immunofluorescence; Spectroscopy; Tubulin-microtubule