Inhibition of catechol-Omicron-methyltransferase activity in human breast cancer cells enhances the biological effect of the green tea polyphenol (-)-EGCG.

Abstract

Tea is one of the most popular beverages in the world and has been studied extensively as a health-promoting beverage that may act to prevent a number of chronic diseases and cancers. (-)-Epigallocatechin gallate [(-)-EGCG], a major component in green tea, is unstable under physiological conditions and methylation of (-)-EGCG by catechol-Omicron-methyltransferase (COMT) is a modification that reduces the biological activity of (-)-EGCG. In the current study, we hypothesized that suppression of COMT activity in human breast cancer cells could increase the proteasome-inhibitory potency of (-)-EGCG and therefore enhance its tumor cell growth-inhibitory activity. We first determined the COMT genotype and basal levels of COMT activity in various human breast cancer cell lines. Furthermore, when breast cancer MDA-MB-231 cells containing high COMT activity were tested, the diminished COMT activity apparently increased the effectiveness of (-)-EGCG via augmented proteasome inhibition and apoptosis induction. This study supplements the previous findings that methylated (-)-EGCG is less bioactive and supports the notion that COMT inhibition may increase the anti-cancer properties of tea polyphenols and the combination may serve as a novel approach or supplemental treatment for breast cancer chemotherapy.

• Authors: Kristin Landis-Piwowar, Di Chen, Tak Hang Chan, Q Ping Dou
• Journal: Oncology reports (Oncol Rep) Vol. 24 Issue 2 Pg. 563-9 (Aug 2010) ISSN: 1791-2431 [Electronic] Greece
• PMID: 20596647 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Catechol O-Methyltransferase Inhibitors
• Enzyme Inhibitors
• Flavonoids
• Phenols
• Polyphenols
• Proteasome Inhibitors
• Tea
• Catechin
• epigallocatechin gallate
• Catechol O-Methyltransferase
• Proteasome Endopeptidase Complex

Topics

• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, pathology)
• Carcinoma (drug therapy, pathology)
• Catechin (administration & dosage, analogs & derivatives, pharmacology)
• Catechol O-Methyltransferase (metabolism, physiology)
• Catechol O-Methyltransferase Inhibitors
• Cell Proliferation (drug effects)
• Drug Evaluation, Preclinical
• Drug Synergism
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (administration & dosage, pharmacology)
• Female
• Flavonoids (administration & dosage, pharmacology)
• Humans
• Phenols (administration & dosage, pharmacology)
• Polyphenols
• Proteasome Endopeptidase Complex (metabolism)
• Proteasome Inhibitors
• Tea (chemistry)
• Tumor Cells, Cultured