Effects of tea polyphenols on signal transduction pathways related to cancer chemoprevention

Hou, Zhe; Lambert, Joshua D.; Chin, Khew‐Voon; Yang, Chung S.

doi:10.1016/j.mrfmmm.2004.06.040

Cited by 139 publications

(107 citation statements)

References 65 publications

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“…When added to the cell culture medium, EGCG is oxidized to produce superoxide radical and H 2 O 2 [55]. We have demonstrated that, depending on the cell lines and culture conditions, the 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 [49]. Autooxidation of EGCG generated reactive species may inactivate epidermal growth factor receptor in cells in culture [55].…”

Section: Mechanistic Studies On the Activities Of Egcg In Cell Linesmentioning

confidence: 91%

“…Many studies on the mechanisms of action of EGCG and other catechins have been conducted in cell lines, and this topic has been reviewed previously [4,48,49]. The proposed mechanisms include inhibition of MAP kinases and the PI3K/AKT pathway, inhibition of NFκB-and AP-1-mediated transcription, inhibition of growth factor-mediated signaling, inhibition of proteinase activities, and other activities.…”

Section: Mechanistic Studies On the Activities Of Egcg In Cell Linesmentioning

confidence: 99%

“…The proposed mechanisms include inhibition of MAP kinases and the PI3K/AKT pathway, inhibition of NFκB-and AP-1-mediated transcription, inhibition of growth factor-mediated signaling, inhibition of proteinase activities, and other activities. The concentrations of EGCG required to observe these biological effects in vitro, however, usually exceed the concentrations achievable in plasma and tissues by 10-to 100-fold, and questions remain concerning the relevance of these in vitro observations to the mechanisms of the cancer-preventive activities in vivo [49].…”

Section: Mechanistic Studies On the Activities Of Egcg In Cell Linesmentioning

confidence: 99%

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Inhibition of carcinogenesis by tea constituents

Lǚ

Lambert

et al. 2007

Seminars in Cancer Biology

126

104

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The possible cancer preventive activity of tea has received much attention in recent years. The inhibitory activities of tea and tea constituents against carcinogenesis at different organ sites have been demonstrated in many animal models. The effect of tea consumption on human cancers, however, remains inconclusive. The mechanisms of action of tea polyphenols, especially EGCG, the most abundant and active catechin, have been extensively investigated. Most of the studies, however, were based on cell culture systems, and these mechanisms need to be evaluated and verified in animal models or humans in order to gain more understanding on the effect of tea consumption on human cancer. Human intervention trials are warranted to determine the possible prevention of cancer of specific sites by preparation of tea constituents.

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Section: Mechanistic Studies On the Activities Of Egcg In Cell Linesmentioning

confidence: 91%

Section: Mechanistic Studies On the Activities Of Egcg In Cell Linesmentioning

confidence: 99%

Section: Mechanistic Studies On the Activities Of Egcg In Cell Linesmentioning

confidence: 99%

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Inhibition of carcinogenesis by tea constituents

Lǚ

Lambert

et al. 2007

Seminars in Cancer Biology

126

104

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“…Different mechanisms of action of these compounds have been proposed, based mainly on studies in various cell line systems. These include inhibition of telomerase activity, mitogen-activated protein kinases, active protein-1 mediated transcription, growth factor-mediated signaling, aberrant arachidonic acid metabolism, and other activities [8]. These events may lead to the inhibition of tumor cell growth or induction of apoptosis as well as the inhibition of angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

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

Sang

Yang

Buckley

et al. 2007

Free Radical Biology and Medicine

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133

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Abstract(−)-Epigallocatechin-3-gallate (EGCG), the most abundant and biologically active compound in tea, has been proposed to have beneficial health effects, including prevention of cancer and heart disease. Different mechanisms of action of EGCG have been proposed, based mainly on studies in cell line systems, in which EGCG is not stable. It has been proposed that oxidation of EGCG and its production of reactive oxygen species are responsible for the biological activities such as receptor inactivation and telomerase inhibition. It is unclear, however, if this phenomenon occurs in vivo. In the present study, the stability of EGCG and product formation in Tris-HCl buffer was investigated using realtime mass spectrometry combined with tandem mass ion mapping. With real-time mass data acquisition, we demonstrate for the first time the formation of EGCG quinone, EGCG dimer quinone, and other related compounds. The structural information of the major appearing ions was provided by tandem mass analysis of each ion. A mechanism for the autoxidation of EGCG was proposed based on the structural information of these ions. None of these oxidation products were observed in the plasma samples of mice after treatment with 50 mg/kg EGCG, i.p. daily for 3 days. Instead, the methylated and conjugated metabolites of EGCG were observed. Therefore the roles of EGCG autoxidation in the biological activities of this compound in vivo remain to be investigated further.

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“…1), have been shown to inhibit tumorigenesis in a number of animal models [1,2]. Numerous mechanisms of action have been proposed, including inhibition of growth factor signaling, inhibition of kinases, inhibition of DNA methyltransferase, and others [3,4]. EGCG undergoes auto-oxidation resulting in oligomerization and the formation of reactive oxygen species (ROS) under cell culture conditions [5,6].…”

Section: Introductionmentioning

confidence: 99%

N-Acetylcysteine enhances the lung cancer inhibitory effect of epigallocatechin-3-gallate and forms a new adduct

Lambert

Sang

Yang

2008

Free Radical Biology and Medicine

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The major tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), inhibits carcinogenesis in many in vivo models. Many potential mechanisms of action have been proposed based on cell line studies, including pro-oxidant activity. In the present study, we studied the effect of N-acetylcysteine (NAC) on the inhibitory effects of EGCG on lung cancer cell growth. We found that NAC (0 -2 mM) dosedependently enhanced the growth inhibitory activity of EGCG against murine and human lung cancer cells. The combination of NAC and EGCG caused an 8.8-fold increase in apoptosis in CL13 mouse and H1299 human lung cancer cells compared to treatment with either agent alone. Addition of 2 mM NAC increased the stability of EGCG in the presence of CL13 cells (t 1/2 = 8.5 h vs. 22.7 h). Intracellular levels of EGCG were increased 5.5-fold by the addition of 2 mM NAC. HPLC and LC-MS analyses of cell culture medium from CL13 cells treated with EGCG and NAC for 24 h revealed that EGCG-2′-NAC was time-dependently formed. This adduct was not formed in the absence of NAC. The present results show that under cell culture conditions, EGCG and NAC interact to form a previously unreported adduct, EGCG-2′-NAC, which may contribute to enhancement of EGCGmediated cell killing.

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Effects of tea polyphenols on signal transduction pathways related to cancer chemoprevention

Cited by 139 publications

References 65 publications

Inhibition of carcinogenesis by tea constituents

Inhibition of carcinogenesis by tea constituents

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

N-Acetylcysteine enhances the lung cancer inhibitory effect of epigallocatechin-3-gallate and forms a new adduct

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