Green tea polyphenols as a natural tumour cell proteasome inhibitor.
The cancer-preventive effects of green tea and its main constituent (-)-epigallocatechin gallate [(-)-EGCG] are widely supported by results from epidemiological, cell culture, animal and clinical studies although the molecular target has not been well defined. We previously reported that ester bond-containing tea polyphenols, e. g. (-)-EGCG, and their synthetic analogs potently and specifically inhibited the proteasomal activity. Subsequently, we further demonstrated that methylation on green tea polyphenols under physiological conditions decreased their proteasome-inhibitory activity, contributing to decreased cancer-preventive effects of tea consumption. Since (-)-EGCG is unstable under physiological conditions, we also developed the peracetate-protected or prodrug form of (-)-EGCG, Pro-EGCG (1), and shown that Pro-EGCG (1) increases the bioavailability, stability, and proteasome-inhibitory and anticancer activities of (-)-EGCG in human breast cancer cells and xenografts, suggesting its potential use for cancer prevention and treatment.
Dou
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The Prevention Program, Barbara Ann Karmanos Cancer Institute and Department of Pathology, School of Medicine, Wayne State University, 540.1 HWCRC, 4100 John R Rd, Detroit, Michigan 48201, USA. doup@karmanos.org
Landis-Piwowar
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Chen
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Huo
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Wan
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Chan
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D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008745:Methylation; D061988:Proteasome Inhibitors; D013662:Tea; D025801:Ubiquitin / Q000378:metabolism
D016588:Anticarcinogenic Agents; D061988:Proteasome Inhibitors; D013662:Tea; D025801:Ubiquitin; D002392:Catechin; C045651:epigallocatechin gallate