Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols

Abstract

In order to study the biological activities of tea preparations and purified tea polyphenols, their growth inhibitory effects were investigated using four human cancer cell lines. Growth inhibition was measured by [3H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) displayed strong growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22 microM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC50 values 2- to 3-fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)-epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H2O2 may mediate apoptosis and that this may contribute to the growth inhibitory activities of tea polyphenols in vitro.

Coffee and tea consumption, genotype-basedCYP1A2andNAT2activity and colorectal cancer risk-Results from the EPIC cohort study

“…41,42 It is hypothesized that tea consumption may lower CRC risk through its antioxidant components protecting colonic epithelial cells against oxidative radicals. 43,44 Despite the consistently observed protective effect of tea components in animal studies, a protective effect has, in general, not been demonstrated in epidemiological studies, 11,13 and is further confirmed by the present study. However, disparities can be observed between findings from Western and Asian studies, which might be caused by differences in type of tea (black or green) consumed.…”

Autoxidative quinone formation in vitro and metabolite formation in vivo from tea polyphenol (-)-epigallocatechin-3-gallate: Studied by real-time mass spectrometry combined with tandem mass ion mapping

“…For example, we have demonstrated that, depending on the cell lines and culture conditions, EGCG-induced apoptosis can be completely or partially blocked by the addition of catalase in the culture medium, suggesting that the apoptosis is mediated by H 2 O 2 [21,22]. We also found that catalase partially blocked EGCG-induced apoptosis and also abolished the effects on TGFβ signaling in transformed human bronchial epithelial cells (21BES) [23].…”

The green tea polyphenol, epigallocatechin‐3‐gallate, protects against the oxidative cellular and genotoxic damage of UVA radiation

“…A difference in the response of the two probes to changes in cellular glutathione status has been reported previously 24 and further suggests that DHR and DCFH possess differing ranges of reactivity. There is an increasing trend to use DCFH or DHR oxidation as evidence of H 2 O 2 production 7,37 and although the probes do react with peroxide, they are sensitive to a variety of other free radical species. 39 The fact that there is an increase in DCFH oxidation in UVA-irradiated, EGCGtreated cells suggests that DCFH may react with reactive species generated as a result of the oxidation of EGCG through scavenging UVA ROS or with an EGCG radical itself.…”

“…[7][8][9] Several mechanisms have been proposed by which these compounds exert their anti-tumorigenic action: these include the blockade of growth factors binding to their receptors, 10 phosphorylation (activation) of mitogen-activated protein kinases (MAPKs) 11,12 possibly resulting in the observed induction of Phase II drug-metabolizing enzymes, 13,14 and the generation of oxidative stress leading to apoptosis. 7,9 In the face of an oxidative challenge, however, it is now well documented that green tea catechins act as antioxidants. For example, EGCG abrogates oxidation by hydrogen peroxide both in a cell free system 15 and in terms of DNA single-strand break damage.…”