A Gene Expression Signature that Can Predict Green Tea Exposure and Chemopreventive Efficacy of Lung Cancer in Mice

Lü, Yan; Yao, Ruisheng; Yan, Yan; Wang, Yian; Hara, Yukihiko; Lubet, Ronald A.; You, Ming

doi:10.1158/0008-5472.can-05-3158

Cited by 33 publications

(34 citation statements)

References 22 publications

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“…The genes that were affected by treatment with green tea and Polyphenon E in a similar carcinogenesis model have been reported by Lu et al (46). Direct targets of EGCG action identified by different methods in other systems have also been reported (47,48).…”

Section: Discussionsupporting

confidence: 64%

Inhibition of Adenoma Progression to Adenocarcinoma in a 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone–Induced Lung Tumorigenesis Model in A/J Mice by Tea Polyphenols and Caffeine

et al. 2006

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The present study investigated the inhibitory effects of Polyphenon E [a standardized green tea polyphenol preparation containing 65% (À)-epigallocatechin-3-gallate] and caffeine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor progression from adenoma to adenocarcinoma. Female A/J mice were treated with a single dose of NNK (103 mg/kg body weight, i.p.) and kept for 20 weeks for the mice to develop lung adenomas. The mice were then given a solution of 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until week 52. Both treatments significantly decreased the number of visible lung tumors. Histopathologic analysis indicated that Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed marginal inhibitory effects in incidence and multiplicity of adenocarcinoma (by 48% and 49%, respectively). Markers of cell proliferation, apoptosis, and related cell signaling were studied by immunohistochemistry, and the labeling index and staining intensity were quantified by the Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively) in adenocarcinomas, enhanced apoptosis in adenocarcinomas (by 2.6-and 4-fold, respectively) and adenomas (both by 2.5-fold), and lowered levels of c-Jun and extracellular signal-regulated kinase (Erk) 1/2 phosphorylation. In the normal lung tissues, neither agent had a significant effect on cell proliferation or apoptosis. The results show that tea polyphenols (and perhaps caffeine) inhibit the progression of NNK-induced lung adenoma to adenocarcinoma. This effect is closely associated with decreased cell proliferation, enhanced apoptosis, and lowered levels of c-Jun and Erk1/2 phosphorylation. (Cancer Res 2006; 66(23): 11494-501)

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Section: Discussionsupporting

confidence: 64%

Inhibition of Adenoma Progression to Adenocarcinoma in a 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone–Induced Lung Tumorigenesis Model in A/J Mice by Tea Polyphenols and Caffeine

et al. 2006

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“…Lu et al [20] recently analyzed the gene expression changes caused by the administration of green tea or PPE to chemically-induced mouse model for lung tumorigenesis. They found that 88 genes that were differentially expressed in tumors (from the normal tissues) were reversed by the treatment and suggested that these genes may be used as markers for tea exposure.…”

Section: Lung Tumorigenesismentioning

confidence: 99%

Inhibition of carcinogenesis by tea constituents

Lǚ

Lambert

et al. 2007

Seminars in Cancer Biology

130

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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“…Finally, we will discuss the relevance of these results in the prevention of human cancer based on human epidemiological and interventions studies. This topic has been covered by previous reviews (Yang and Wang, 1993;Bushman, 1998;Yang et al, 2002;Hou et al, 2004;Lambert et al, 2005;Clark and You, 2006;Khan et al, 2006;Lu et al, 2006b;Sun et al, 2006b;Sun et al, 2006a;Wu and Yu, 2006;Yang et al, 2006a;Yang et al, 2006b). Because of the citation limitations, we will cite the key reviews instead of some of the original articles.…”

Section: Introductionmentioning

confidence: 99%

Tea and cancer prevention: Molecular mechanisms and human relevance

Yang

Lambert

et al. 2007

Toxicology and Applied Pharmacology

240

169

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Tea made from the leaves of the plant Camellia sinensis is a popular beverage. The possible cancer preventive activity of tea and tea polyphenols has been studied extensively. This article briefly reviews studies in animal models, cell lines, and possible relevance of these studies to the prevention of human cancer. The cancer preventive activity of tea constituents have been demonstrated in many animal models including cancer of the skin, lung, oral cavity, esophagus, stomach, liver, pancreas, small intestine, colon, bladder, prostate, and mammary gland. The major active constituents are polyphenols, of which (-)-epigallocatechin-3-gallate (EGCG) is most abundant, most active, and most studied, and caffeine. The molecular mechanisms of the cancer preventive action, however, are just beginning to be understood. Studies in cell lines led to the proposal of many mechanisms on the action of EGCG. However, mechanisms based on studies with very high concentrations of EGCG may not be relevant to cancer prevention in vivo. The autooxidation of EGCG in cell culture may also produce activities that do not occur in many internal organs. In contrast to the cancer prevention activity demonstrated in different animal models, no such conclusion can be convincingly drawn from epidemiological studies on tea consumption and human cancers. Even though the human data are inconclusive, tea constituents may still be used for the prevention of cancer at selected organ sites if sufficient concentrations of the agent can be delivered to these organs. Some interesting examples in this area are discussed.

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A Gene Expression Signature that Can Predict Green Tea Exposure and Chemopreventive Efficacy of Lung Cancer in Mice

Abstract: Green tea has been shown to be a potent chemopreventive agent against lung tumorigenesis in animal models. Previously, we found that treatment of A/J mice with either green tea (0.6% in water)

Cited by 33 publications

References 22 publications

Inhibition of Adenoma Progression to Adenocarcinoma in a 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone–Induced Lung Tumorigenesis Model in A/J Mice by Tea Polyphenols and Caffeine

Inhibition of Adenoma Progression to Adenocarcinoma in a 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone–Induced Lung Tumorigenesis Model in A/J Mice by Tea Polyphenols and Caffeine

Inhibition of carcinogenesis by tea constituents

Tea and cancer prevention: Molecular mechanisms and human relevance

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