title: Green tea catechins in chemoprevention of cancer: a molecular docking investigation into their interaction with glutathione S-transferase (GST P1-1).
abstract: The anti- and pro-oxidant effects of green tea catechins have been implicated in the alterations of cellular functions determining their chemoprotective and therapeutic potentials in toxicity and diseases. The glutathione S-transferases (GSTs; EC 2.5.1.18) family is a widely distributed phase-II detoxifying enzymes and the GST P1-1 isoenzyme has been shown to catalyze the conjugation of GSH with some alkylating anti-cancer agents, suggesting that over-expression of GST P1-1 would result in tumor cell resistance. Here we report the docking study of four green tea catechins and four alkylating anticancer drugs into the GST P1-1 model, as GSTs were found to be affected by tea catechins. The EGCG ligands exhibit higher docking potential with respect to the anticancer agents, with a ligand-receptor interaction pattern indicating an high conformational stability. Consequently, the competition mechanisms favourable for the green tea catechins could lead to enzyme(s) desensitisation with a reduction of the alkylating drugs metabolism. The results provide a useful theoretical contribution in understanding the biochemical mechanisms implicated in the chemotherapeutic use of green tea catechins in oxidative stress-related diseases.
authors.affiliation: Faculty of Pharmacy, Istituto di Chimica Farmaceutica e Tossicologica "Pietro Pratesi", University of Milan, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Artali
authors.forename: Giangiacomo
authors.initials: G
authors.lastname: Beretta
authors.forename: Paolo
authors.initials: P
authors.lastname: Morazzoni
authors.forename: Ezio
authors.initials: E
authors.lastname: Bombardelli
authors.forename: Fiorella
authors.initials: F
authors.lastname: Meneghetti
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000378:metabolism*; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology*; D018890:Chemoprevention; D003198:Computer Simulation; D019008:Drug Resistance, Neoplasm; D005978:Glutathione; D005982:Glutathione Transferase / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D013662:Tea
chemical_list: D018906:Antineoplastic Agents, Alkylating; D013662:Tea; D002392:Catechin; D005982:Glutathione Transferase; D005978:Glutathione