Green tea polyphenols as a natural tumour cell proteasome inhibitor
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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.
Keywords:Tea polyphenols Proteasome inhibitors Molecular target Methylation Prodrug Cancer prevention Chemotherapy
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