Certain (−)-epigallocatechin-3-gallate (EGCG) auto-oxidation products (EAOPs) retain the cytotoxic activities of EGCG

• Published in: Food chemistry 2016-08, Vol.204, p.218-226
• Main Authors: Wei, Yaqing, Chen, Pingping, Ling, Tiejun, Wang, Yijun, Dong, Ruixia, Zhang, Chen, Zhang, Longjie, Han, Manman, Wang, Dongxu, Wan, Xiaochun, Zhang, Jinsong
• Format: Article
• Language: English
• Subjects: Animals; Anticarcinogenic Agents - chemistry; Anticarcinogenic Agents - pharmacology; Auto-oxidation; Camellia sinensis - chemistry; Catechin - analogs & derivatives; Catechin - chemistry; Catechin - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chromatography, High Pressure Liquid; Cysteine - metabolism; Cytotoxic activity; Dose-Response Relationship, Drug; EGCG; Humans; Hydrogen peroxide; Hydrogen Peroxide - analysis; Mice; Oxidation-Reduction; Plant Leaves - chemistry; Sulfhydryl group; Tea - chemistry; Thioredoxin-Disulfide Reductase - antagonists & inhibitors
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2016.02.134

•EGCG auto-oxidation products (EAOPs) are unstable.•EAOPs gain an enhanced capacity to deplete cysteine thiol groups.•EGCG auto-oxidation does not necessarily compromise its cytotoxicity.•EGCG and EAOPs work in concert to exert cytotoxic effects. (−)-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.