Green Tea Extract Inhibition of Human Leiomyoma Cell Proliferation Is Mediated via Catechol-<b><i>O</i></b>-Methyltransferase

Abstract

Background/Aims: To investigate the inhibitory effect of green tea extract, epigallocatechin gallate (EGCG), on wild-type human leiomyoma (WT-HuLM) cells and its potential action via catechol-o-methyltransferase (COMT) activity. Methods: Cell proliferation of WT-HuLM and COMT gene-silenced HuLM (COMT-shRNA-HuLM) cells treated with 0 or 100 µ<smlcap>M</smlcap> EGCG for 7 days was measured using the MTT method. Total RNA and protein were extracted from cells treated with 0 or 100 µ<smlcap>M</smlcap> of EGCG for 48 h. Gene expression profiling was performed using Human Signal Transduction PathwayFinder. Proliferation cell nuclear antigen (PCNA), cyclin-dependent kinase 4 (Cdk4) and COMT protein levels were detected by Western blot analyses. COMT enzyme activity was evaluated by HPLC. Results: EGCG-treated WT-HuLM cells showed significantly decreased COMT expression (p < 0.001) and enzyme activity (p < 0.05) compared to untreated WT-HuLM cells, while COMT-shRNA-HuLM cells showed no significant change. At 100 μ<smlcap>M</smlcap> of EGCG, survival of WT-HuLM cells was significantly lower (p < 0.05) compared to COMT-shRNA-HuLM cells. EGCG treatment modulated multiple signaling pathways in WT-HuLM compared to untreated control, while changes were minimal or reversed in COMT-shRNA-HuLM cells. EGCG significantly decreased PCNA, Cdk4 and soluble COMT protein levels (p < 0.001) in WT-HuLM, but not in COMT-shRNA-HuLM cells. Conclusions: The antiproliferative and gene-modulating effects of EGCG on HuLM cells are mediated, at least partially, via its effect on COMT expression and enzyme activity.

Dietary Natural Compounds and Vitamins as Potential Cofactors in Uterine Fibroids Growth and Development

“…The average daily intake of EGCG from green tea consumption in the EU ranges from 90 to 300 mg/day, while high-level consumers intake even up to 860 mg EGCG/day. In vitro studies showed that EGCG, consumed in the form of a green tea extract, inhibited proliferation and growth and promoted apoptosis in cultures of human uterine leiomyoma cells in a dose-dependent manner [94,95]. Antiproliferative and gene-modulating effects of EGCG were partially mediated through the effect on catechol-O-methyltransferase (COMT) enzyme activity.…”

The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium

“…D (whose influence on COMT has been reported [123]), vit. D supplementation, consumption of large quantities of green tea, or supplementation of its extracts [124].…”

Biological and Mechanistic Characterization of Novel Prodrugs of Green Tea Polyphenol Epigallocatechin Gallate Analogs in Human Leiomyoma Cell Lines

“…These data support our hypothesis, and suggest that UtLM‐ht cells express active COMT, and that COMT is involved in regulating the sensitivity of cells to EGCG‐based therapy. Zhang et al [] also demonstrated the presence of active COMT in a human uterine leiomyoma cell line; however, their conclusions are obfuscated by their use of non‐physiological concentrations of EGCG (100 μM). Consistent with the study reported here, we have previously shown that DNC treatment increases the biological activity of EGCG and Pro‐EGCG in human breast cancer MDA‐MB‐231 cells—a cell line with a high level of COMT activity [Huo et al, ; Landis‐Piwowar et al, ].…”