Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: Teratogenicity and reproductive toxicity studies in rats

Isbrucker, Richard; Edwards, John S.; Wolz, E.; Davidovich, A.; Bausch, Jochen

doi:10.1016/j.fct.2005.11.002

Cited by 110 publications

(72 citation statements)

References 12 publications

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“…All of the seven botanical compounds tested were able to inhibit cell growth in the mouse prostate cancer cell line TRAMP-C2, with IC 50 50 of <1 μmol/L, resveratrol was the most potent, followed by apigenin, baicalein, and cyclopamine. Curcumin was the most effective, reaching a maximal inhibition of 95%, followed by cyclopamine with 85%.…”

Section: Resultsmentioning

confidence: 99%

Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer

et al. 2010

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Many botanical compounds have been proposed to prevent cancer. We investigated the cancer treatment and prevention abilities of apigenin, baicalein, curcumin, epigallocatechin 3-gallate (EGCG), genistein, quercetin, and resveratrol both in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice as well as in vitro in prostate cancer cell lines. In our experiments, these seven compounds act similarly to the Hedgehog antagonist cyclopamine, a teratogenic plant alkaloid, which had been previously shown to "cure" prostate cancer in a mouse xenograft model. With IC 50 values ranging from <1 to 25 μmol/L, these compounds can inhibit Gli1 mRNA concentration by up to 95% and downregulate Gli reporter activity by 80%. We show that four compounds, genistein, curcumin, EGCG, and resveratrol, inhibit Hedgehog signaling as monitored by real-time reverse transcription-PCR analysis of Gli1 mRNA concentration or by Gli reporter activity. Three compounds, apigenin, baicalein, and quercetin, decreased Gli1 mRNA concentration but not Gli reporter activity. Our results show that these compounds are also able to reduce or delay prostate cancer in vivo in TRAMP mice. All seven compounds, when fed in combination as pure compounds or as crude plant extracts, inhibit well-differentiated carcinoma of the prostate by 58% and 81%, respectively. In vitro, we show that all seven compounds also inhibit growth in human and mouse prostate cancer cell lines. Mechanistically, we propose the Hedgehog signaling pathway to be a direct or indirect target of these compounds. These botanicals at pharmacologic concentrations are potentially safer and less expensive alternatives to cyclopamine and its pharmaceutical analogues for cancer therapy. Cancer Res; 70(8); 3382-90. ©2010 AACR.

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Section: Resultsmentioning

confidence: 99%

Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer

et al. 2010

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“…In animal experiments, a daily dose of up to ~1,000 mg/kg EGCG did not show teratogenicity in rats [189]. A topical dose of 1,860 mg/kg of EGCG resulted in minor dermal irritation in rats and guinea pigs but not in rabbits [190].…”

Section: Effects On Ttr Toxicity In Vivomentioning

confidence: 99%

Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01

Attar

Rahimi

Bitan

2013

Translational Neuroscience

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Abnormal protein folding and self-assembly causes over 30 cureless human diseases for which no diseasemodifying therapies are available. The common side to all these diseases is formation of aberrant toxic protein oligomers and amyloid fibrils. Both types of assemblies are drug targets, yet each presents major challenges to drug design, discovery, and development. In this review, we focus on two small molecules that inhibit formation of toxic amyloid protein assemblies -the green-tea derivative (-)-epigallocatechin-3-gallate (EGCG), which was identified through a combination of epidemiologic data and a compound library screen, and the molecular tweezer CLR01, whose inhibitory activity was discovered in our group based on rational reasoning, and subsequently confirmed experimentally. Both compounds act in a manner that is not specific to one particular protein and thus are useful against a multitude of amyloidogenic proteins, yet they act via distinct putative mechanisms. CLR01 disrupts protein aggregation through specific binding to lysine residues, whereas the mechanisms underlying the activity of EGCG are only recently beginning to unveil. We discuss current in vitro and, where available, in vivo literature related to EGCG and CLR01's effects on amyloid β-protein, α-synuclein, transthyretin, islet amyloid polypeptide, and calcitonin. We also describe the toxicity, pharmacokinetics, and mechanism of action of each compound.

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“…The US Dietary Supplement Information Expert Committee (DSIEC) further suggested that green tea is a very popular beverage and yet seldom shows liver toxicity, and listed it in a safety level of 2 (Sarma et al, 2008). Research findings from Japan and UK as well as a report from Switzerland concluded that catechin does not produce genotoxicity nor show liver toxicity (Isbrucker et al, 2006a;2006b;2006c;Ogura et al, 2008). A study on the oral administration in mice conducted in Taiwan reported that it was safe even at a very high dosage of 2500 mg/(kg·d) (which corresponds to a human weighing 60 kg taking 150 g green tea extracts daily) (Hsu et al, 2011).…”

Section: Concerns On the Safety Of Tea Polyphenolsmentioning

confidence: 99%

Tea and human health: biomedical functions of tea active components and current issues

Chen

Zhi

2015

J. Zhejiang Univ. Sci. B

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Originating in China, tea and tea planting have spread throughout the world since the middle of the Tang dynasty. Now people from 160 countries in the world are accustomed to tea drinking. A brief history of tea's medicinal role in China and its spread to the world are introduced. The effectiveness of tea active components and tea drinking on major human diseases, including cancer, metabolic syndrome, cardiovascular disease, and neurodegenerative diseases, is discussed. Also presented are some related issues, such as the bioavailability of tea active components, the new formulations of tea polyphenols, and the safety for consumers of dietary supplements containing tea polyphenols.

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Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: Teratogenicity and reproductive toxicity studies in rats

Cited by 110 publications

References 12 publications

Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer

Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer

Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01

Tea and human health: biomedical functions of tea active components and current issues

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