Journal
ONCOLOGY REPORTS
Volume 24, Issue 2, Pages 563-569Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or_00000893
Keywords
epigallocatechin gallate; catechol-O-methyltransferase; proteasome inhibition; apoptosis; breast cancer
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Funding
- National Cancer Institute [1R01CA120009, 3R01CA120009-04S1]
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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-O-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.
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