Inhibition of catechol-Omicron-methyltransferase activity in human breast cancer cells enhances the biological effect of the green tea polyphenol (-)-EGCG.
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.
Landis-Piwowar
Kristin
K
Department of Pathology, Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
Chen
Di
D
Chan
Tak Hang
TH
Dou
Q Ping
QP
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000378:metabolism / Q000502:physiology; D065098:Catechol O-Methyltransferase Inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology; D059808:Polyphenols; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D013662:Tea / Q000737:chemistry; D014407:Tumor Cells, Cultured
D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D061988:Proteasome Inhibitors; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D002394:Catechol O-Methyltransferase; D046988:Proteasome Endopeptidase Complex