title: Identification of an EGCG oxidation derivative with proteasome modulatory activity.
abstract: (-)-epigallocatechin-3-gallate (EGCG) has been shown to possess chemopreventative properties and the ability to inhibit proteasome, a multicatalytic protease involved in the removal of oxidized and misfolded proteins and in the turnover of important checkpoint proteins. The stability of EGCG under neutral-alkaline and cellular physiological conditions was evaluated, identifying a biologically active ring-fission oxidative product. This derivative differentially affected proteasome activities with respect to EGCG in vitro, whereas, in cervical carcinoma cells, both compounds inhibited proteasome functionality to a similar extent, promoting a significant accumulation of ubiquitinated proteins and apoptotic markers. Despite of EGCG high instability, an equally active metabolite, able to modulate both proteasome functionality and apoptotic pathways, is generated. Interestingly this derivative protracts both the EGCG antioxidant and proteasome modulating efficacy, irrespective of the catechin short half-life.
authors.affiliation: University of Camerino, School of Biosciences and Biotechnology, via Gentile III da Varano, 62032 Camerino (MC), Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bonfili
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cuccioloni
authors.forename: Matteo
authors.initials: M
authors.lastname: Mozzicafreddo
authors.forename: Valentina
authors.initials: V
authors.lastname: Cecarini
authors.forename: Mauro
authors.initials: M
authors.lastname: Angeletti
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Eleuteri
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011485:Protein Binding; D050050:Protein Carbonylation; D011506:Proteins / Q000378:metabolism; D013499:Surface Properties; D054875:Ubiquitination
chemical_list: D000975:Antioxidants; D061988:Proteasome Inhibitors; D011506:Proteins; D002392:Catechin; C045651:epigallocatechin gallate; D046988:Proteasome Endopeptidase Complex