EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells

Jung, Young Do; Kim, M. S.; Shin, Boo Ahn; Chay, Kee-Oh; Ahn, Bong Whan; Liu, W.; Bucana, Corazon D.; Gallick, Gary E.; Ellis, Lee M.

doi:10.1054/bjoc.2000.1691

Cited by 299 publications

(194 citation statements)

References 28 publications

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“…New data (Cao et al, 1999) indicate that EGCG suppresses endothelial cell growth in vitro and the formation of new blood vessels in chick chorioallantoic membrane; drinking green tea significantly prevents corneal vascularisation induced by one of the most potent angiogenetic factors (VEGF). The same results have been obtained by Jung et al (2001) in in vitro studies, in serum-deprived HT29 cells, and in in vivo studies, on the growth of HT29 cells in nude mice. EGCG exerts, at least part of its anticancer effect, by inhibiting angiogenesis through blocking the induction of VEGF in both in vitro and in vivo studies, while EGC, ECG and EC have not demonstrated the same effect (Jung et al, 2001).…”

supporting

confidence: 82%

Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2)

Salucci¹,

Stivala

Maiani³

et al. 2002

Br J Cancer

160

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Green tea, mainly through its constituents epigallocatechin gallate, epigallocatechin, epicatechin gallate and epicatechin, has demonstrated anticarcinogenic activity in several animal models, including those for skin, lung and gastro-intestinal tract cancer, although less is known about colorectal cancer. Quercetin, the major flavonoid present in vegetables and fruit, exerts potential anticarcinogenic effects in animal models and cell cultures, but less is known about quercetin glucosides. The objectives of this study were to investigate (i) the antioxidant activity of the phenolic compounds epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside; (ii) the cytotoxicity of different concentrations of epicatechin, epigallocatechin gallate, and gallic acid; (iii) the cellular uptake of epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside and (iv) their effect on the cell cycle. Human colon adenocarcinoma cells were used as experimental model. The results of this study indicate that all dietary flavonoids studied (epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside) show a significant antioxidant effect in a chemical model system, but only epigallocatechin gallate or gallic acid are able to interfere with the cell cycle in Caco2 cell lines. These data suggest that the antioxidant activity of flavonoids is not related to the inhibition of cellular growth. From a structural point of view, the galloyl moiety appears to be required for both the antioxidant and the antiproliferative effects. Epidemiological studies from around the world have consistently reported that a high intake of fruit and vegetables is associated with a low incidence of most types of cancer (Wang et al, 1989;Dragsted et al, 1993). It is estimated that about 70% of all cancers are attributable to the diet. Colorectal cancer is the second most prevalent cancer in the developed world (Parkin et al, 1985). Western diet with a high intake of calories from fat and low fibre supply has been linked to an increase of colon cancer incidence, whilst vegetarian or mediterranean diets are more protective (Vargas and Alberts, 1992). Several compounds have been identified in plants which have well recognised antioxidant properties, such as carotenoids, ascorbic acid, a-tocopherol and flavonoids (Block et al, 1992;Hertog et al, 1992) and inhibit cancer development.Thus, the use of natural substances, that are derived from the diet for chemoprevention, might provide a strategy to inhibit the development of cancer. Green tea, mainly through its constituents epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC), has demonstrated anticarcinogenic activity in several animal models, including those for skin, lung and gastro-intestinal tract cancer (Katiyar et al, 1992;Yang and Wang, 1993). Several recent studies (Berger et al, 2001;Uesato et al, 2001) on the effect of green tea polyphenolics on colon cancer cell lines have shown antiproliferative acti...

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supporting

confidence: 82%

Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2)

Salucci¹,

Stivala

Maiani³

et al. 2002

Br J Cancer

160

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“…16,33 As noted earlier, EGCG is present in feces but undetectable in urine. Thus, our observed EGC-colon cancer association may reflect, at least in part, a major direct role of EGCG in colon cancer protection in humans.…”

Section: Discussionmentioning

confidence: 72%

Urinary biomarkers of tea polyphenols and risk of colorectal cancer in the Shanghai Cohort Study

Yuan

Gao

Yang

et al. 2006

Intl Journal of Cancer

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There have been no studies on specific tea polyphenol biomarkers and risk of colorectal cancer in humans. We prospectively examined the associations between validated biomarkers of specific tea polyphenols and risk of developing colorectal cancer among a cohort of 18,244 men in Shanghai, China, with 16 years of followup. Epigallocatechin (EGC), 4 0 -O-methyl-epigallocatechin (4 0 -MeEGC) and epicatechin, and their metabolites in baseline urine samples were measured on 162 incident colorectal cancer cases and 806 matched controls. Individuals with high prediagnostic urinary EGC levels had a lower risk of colon cancer. Compared with undetectable EGC, odds ratios (95% confidence interval) for colon cancer in the lowest, intermediate and highest tertile of detectable EGC were 0.64 (0.33-1.24), 0.60 (0.30-1.20) and 0.40 (0.19-0.83), respectively (p for trend 5 0.02). A similar inverse relation between 4 0 -MeEGC and colon cancer also was observed. Compared with the lowest quartile, odds ratios (95% confidence intervals) for colon cancer in the 2nd, 3rd and 4th quartiles of urinary 4 0 -MeEGC were 0.49 (0.25-0.96), 0.32 (0.16-0.67) and 0.41 (0.20-0.84), respectively (p for trend 5 0.006). The strongest protective effect was seen for regular tea drinkers who showed high levels of urinary EGC and 4 0 -MeEGC. No association between urinary levels of epicatechin or its metabolite and colon cancer risk was observed. Urinary levels of tea polyphenols and their metabolites were not associated with rectal cancer risk. The present study supports the notion of tea catechins as chemopreventive agents against the development of colon cancer in humans. ' 2006 Wiley-Liss, Inc.Key words: tea; polyphenols; catechins; colorectal cancer Colorectal cancer is the third most common cancer in the United States. 1 The age-standardized (world-population) incidence rates (per 100,000 per year) of colorectal cancer in 1992-1998 were 57.8 in men and 36.7 in women in the United States. 2 In Shanghai, China, a low-risk population for colorectal cancer, the incidence rate increased by 50% in both men and women from the early 1970s to the late 1990s. This rate increase is primarily due to the increasing incidence rate of colon cancer. [3][4][5] It is widely believed that this rapid increase in risk of colon cancer is due to the adoption of a ''western'' diet (i.e. high-fat, high-meat but low-fiber diet) and reduced physical activity by Chinese as a consequence of the country's rapid industrialization and rising affluence over the past 20 years. Although the incidence rate of colorectal cancer has been increasing in native Chinese, they remain at lower risk for colorectal cancer than their Western counterparts; the age-standardized incidence rates (per 100,000 per year) of colorectal cancer in 1993-1997 were 20.3 in men and 19.3 in women in Shanghai, China, about one-half to one-third the comparable rates in the US. 2,5 Tea is made from leaves of the plant Camellia sinensis. About 78% of tea production worldwide is black tea, which is the main tea ...

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“…Recent studies have established that 2 can act as a potential anti-angiogenic compound. [27][28][29][30][31][32] In the present study, 2 (100 μM) moderately activated HIF-1 under normoxic conditions and did not inhibit hypoxia-induced HIF-1 activation. Chemical stability studies suggest that the lack of stability of 2 in this cell-based in vitro system may contribute to its relatively weak HIF-1 regulatory activity.…”

mentioning

confidence: 76%

Hypoxia-Inducible Factor-1 Activation by (−)-Epicatechin Gallate: Potential Adverse Effects of Cancer Chemoprevention with High-Dose Green Tea Extracts

Zhou

Kim

et al. 2004

J. Nat. Prod.

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Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that induces oxygen-regulated genes in response to reduced oxygen conditions (hypoxia). Expression of the oxygen regulated HIF-1α subunit correlates positively with advanced disease stages and poor prognosis in cancer patients. Green tea catechins are believed to be responsible for the cancer chemopreventive activities of green tea. We found that (−)-epicatechin-3-gallate (ECG, 1), one of the major green tea catechins, strongly activates HIF-1 in T47D human breast carcinoma cells. Among the green tea catechins tested, 1 demonstrated the strongest HIF-1 inducing activity while (−)-epigallocatechin-3-gallate (EGCG, 2), was significantly less active. However, 2 is relatively unstable in the in vitro system studied. Compound 1 also increases the expression of HIF-1 target genes including GLUT-1, VEGF, and CDKN1A. In T47D cells, 1 induces nuclear HIF-1α protein without affecting HIF-1α mRNA. Both the induction of HIF-1α protein and activation of HIF-1 by 1 can be blocked by iron and ascorbate, indicating that 1 may activate HIF-1 through the chelation of iron. These results suggest that intended cancer chemoprevention with high-dose green tea extracts may be compromised, by the ability of tea catechins to promote tumor cell survival pathways associated with HIF-1 activation.Rapid tumor growth often outstrips the ability of blood vessels to supply oxygen and nutrients, leaving many regions inside solid tumors low in oxygen (hypoxia). In cancer patients, the extent of tumor hypoxia correlates positively with advanced disease stages, poor prognosis, and treatment resistance. 1 Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a critical role in hypoxia activated gene expression. 2 In tumor cells, HIF-1 activates the transcription of genes involved in anaerobic metabolism, angiogenesis, survival, invasion/metastasis and treatment resistance, thus promoting cellular This study investigates the effects of green tea catechins and related compounds on HIF-1 activity in vitro. Among the compounds tested [1-4, (+)-catechin (5), and gallic acid (6)], only catechins that contain the 3-gallate moiety (1 and 2) activate HIF-1 in a T47D cellbased reporter assay. In addition, 1 inhibits HIF-1 activation under hypoxic conditions. Apart from one hydroxyl group, 1 and 2 are structurally identical. However, 2 is chemically less stable than 1. The focus of this study is the regulation of HIF-1 activity by ECG (1). The pathways and mechanisms involved in HIF-1 activation have been extensively studied. 1,2,9 In the presence of oxygen, the HIF-1α subunit is prolyl hydroxylated, recognized by an E3 ubiquitin ligase complex that contains the von Hippel-Lindau tumor suppressor protein (pVHL), polyubiquitylated, and degraded by the 26S proteosome. [15][16][17] The HIF-1α protein is also asparaginyl hydroxylated to prevent HIF-1 activation. 18 At reduced cellular oxygen levels, inhibition of HIF-1α protein prolyl hydroxylation and degradation leads to an ...

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EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells

Cited by 299 publications

References 28 publications

Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2)

Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2)

Urinary biomarkers of tea polyphenols and risk of colorectal cancer in the Shanghai Cohort Study

Hypoxia-Inducible Factor-1 Activation by (−)-Epicatechin Gallate: Potential Adverse Effects of Cancer Chemoprevention with High-Dose Green Tea Extracts

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