Green tea extract and (−)‐epigallocatechin‐3‐gallate, the major tea catechin, exert oxidant but lack antioxidant activities

Abstract

Green tea is the most widely consumed beverage. It has attained high reputation as a health-promoting dietary component ascribed to the antioxidant activity of (-)-epigallocatechin-3-gallate (EGCG), its main polyphenolic constituent. Evidence is increasing that tea constituents can be cell damaging and pro-oxidant themselves. These effects were suggested to be due to spontaneous H2O2 generation by polyphenols in solution. In the present study, we investigated the oxidant and antioxidant properties of green tea extracts (GTE) and of EGCG by means of the rodent macrophage-like RAW 264.7 and human promyelocytic leukemic HL60 cell lines. The results obtained show that both under cell-free conditions and in the presence of cells the oxidant activities of GTE and EGCG exceeded those of spontaneously generated H2O2 (FOX assay). Increase of intracellular oxidative stress was indicated by 2',7'-dichlorofluorescin probing, and the enhanced genotoxicity was demonstrated by the alkaline comet assay and by the micronucleus assay (cytokinesis block). Time- and dose-dependent induction of cell death was monitored by trypan blue exclusion, MTT assay, and Hoechst staining. Furthermore, in our systems in vitro, EGCG neither directly scavenges H2O2 nor mediates other antioxidant activities but rather increased H2O2-induced oxidative stress and DNA damage. In conclusion, our data suggest that detailed mechanistic studies on the effects of GTE and EGCG should be performed in vivo before excessive intake and/or topical application of green tea products can be recommended to healthy and/or diseased persons.

Epigallocatechin Gallate, a Green Tea Polyphenol, Mediates NO-dependent Vasodilation Using Signaling Pathways in Vascular Endothelium Requiring Reactive Oxygen Species and Fyn

“…In the case of EGCG, there may be unidentified specific cell surface receptors for EGCG that are involved in generation of ROS. However, another possibility is that EGCG may directly generate ROS (including H 2 O 2 ) in a receptor-independent fashion either by autoxidation (64) or by acting as a pro-oxidant in vivo at physiological pH (65). Thus, despite many claims that EGCG is an antioxidant in vitro (66), beneficial bioactivity of EGCG may in fact depend on its ability to behave as a pro-oxidant in physiological contexts that initiates acute intracellular signaling events such as those described in the present study.…”

The roles of polyphenols in cancer chemoprevention

“…High dosages of EGCG can induce DNA damage [41,103,124] due to the generation of hydrogen peroxide. A recent study showed that EGCG neither directly scavenges hydrogen peroxide nor mediates other antioxidant activities, but instead increases hydrogen-peroxide-induced oxidative stress and DNA damage in vitro [19]. EGCG causes oxidative damage to isolated and cellular DNA [23].…”

trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways

“…Detection of intracellular ROS was performed as previously described [9]. Briefly, cells were incubated with 50 lM 2',7'-dichlorodihydrofluorescein diacetate (DHCF-DA) (Molecular Probes, Eugene, OR, USA) (dissolved in dimethyl sulfoxide) for 30 min at 37°C followed by treatment with trans-resveratrol.…”

“…Previous studies have indicated that some nutraceuticals exhibit potent anti-tumor properties and can modulate apoptosis, differentiation and cell cycle, probably by virtue of their anti-oxidant functions. However, in vitro experiments reported that most of them behave as potent pro-oxidants molecules [6,9,40]. For example, organosulfur molecules from garlic, such as the oil-soluble diallyl disulfide [12,13], diallyl trisulfide [22], or the water-soluble S-allylmercaptocysteine [63] have been demonstrated to induce growth arrest and apoptosis dose-dependently by increasing ROS production.…”