title: Certain (-)-epigallocatechin-3-gallate (EGCG) auto-oxidation products (EAOPs) retain the cytotoxic activities of EGCG.
abstract: (-)-Epigallocatechin-3-gallate (EGCG) from green tea has anti-cancer effect. The cytotoxic actions of EGCG are associated with its auto-oxidation, leading to the production of hydrogen peroxide and formation of numerous EGCG auto-oxidation products (EAOPs), the structures and bioactivities of them remain largely unclear. In the present study, we compared several fundamental properties of EGCG and EAOPs, which were prepared using 5mg/mL EGCG dissolved in 200mM phosphate buffered saline (pH 8.0 at 37°C) and normal oxygen partial pressure for different periods of time. Despite the complete disappearance of EGCG after the 4-h auto-oxidation, 4-h EAOPs gained an enhanced capacity to deplete cysteine thiol groups, and retained the cytotoxic effects of EGCG as well as the capacity to produce hydrogen peroxide and inhibit thioredoxin reductase, a putative target for cancer prevention and treatment. The results indicate that certain EAOPs possess equivalent cytotoxic activities to EGCG, while exhibiting simultaneously enhanced capacity for cysteine depletion. These results imply that EGCG and EAOPs formed extracellularly function in concert to exhibit cytotoxic effects, which previously have been ascribed to EGCG alone.
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, Anhui 230036, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, Anhui 230036, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, Anhui 230036, China; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Ling
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, Anhui 230036, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, Anhui 230036, China.
authors.forename: Ruixia
authors.initials: R
authors.lastname: Dong
authors.affiliation: Department of Stomatology, Anhui Medical College, Anhui 230000, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, Anhui 230036, China.
authors.forename: Longjie
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, Anhui 230036, China.
authors.forename: Manman
authors.initials: M
authors.lastname: Han
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, Anhui 230036, China.
authors.forename: Dongxu
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, Anhui 230036, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, Anhui 230036, China. Electronic address: zjs@ahau.edu.cn.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry* / Q000494:pharmacology; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D051379:Mice; D010084:Oxidation-Reduction; D018515:Plant Leaves / Q000737:chemistry; D013662:Tea / Q000737:chemistry; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors
chemical_list: D016588:Anticarcinogenic Agents; D013662:Tea; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D013880:Thioredoxin-Disulfide Reductase; D003545:Cysteine
keywords: Auto-oxidation; Cytotoxic activity; EGCG; Hydrogen peroxide; Sulfhydryl group