Antiproliferative and proapoptotic effects of epigallocatechin gallate on human leiomyoma cells
Dong Zhang, Mohamed Al-Hendy, Gloria Richard-Davis, Valerie Montgomery-Rice, Veera Rajaratnam, Ayman Al-Hendy, Dong Zhang, Mohamed Al-Hendy, Gloria Richard-Davis, Valerie Montgomery-Rice, Veera Rajaratnam, Ayman Al-Hendy
Abstract
Objective: To investigate the effects of epigallocatechin gallate (EGCG), an extract of green tea on cultured human leiomyoma cells (HuLM).
Design: Laboratory study.
Setting: University hospitals.
Patient(s): Not applicable.
Intervention(s): Not applicable.
Main outcome measure(s): The HuLM cells were treated with various EGCG concentrations. Cell proliferation was assayed using Hoechst 33258 dye, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Total RNA was isolated, and gene expression profiling was performed on 84 key genes related to 18 different signal transduction pathways. The protein levels of PCNA, CDK4, BCL2, and BAX were examined by Western blot analysis.
Result(s): The HuLM cells treated with EGCG showed a dose-dependent and time-dependent inhibition of cell proliferation. The TUNEL staining indicated a significant increase in apoptosis in HuLM cells treated with 100 μM of EGCG compared with untreated control. Gene expression profiling indicated that EGCG treatment up-regulated representative genes from the transforming growth factor β (TGF-β) and stress pathways, while inhibiting the survival pathway and NFκB-dependent inflammatory pathway. Western blot analysis confirmed that EGCG at ≥50 μM significantly decreased the expression of PCNA, CDK4, and BCL2 as well as increased the expression of the proapoptotic BAX in a dose-dependent manner.
Conclusion(s): Epigallocatechin gallate inhibits the proliferation of HuLM cells and induces apoptosis. These results suggest that EGCG may be a potential anti-uterine fibroid agent acting through multiple signal transduction pathways.
Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Figures
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EGCG-mediated apoptosis in HuLM cells…
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EGCG-mediated apoptosis in HuLM cells assessed by TUNEL staining (green fluorescence- panel A).…
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Effect of EGCG treatment on…
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Effect of EGCG treatment on the expression of genes related to multiple signal…
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Western blot analysis detecting the…
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Western blot analysis detecting the effects of various EGCG concentrations on pro-apoptosis and…
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- Research Support, N.I.H., Extramural
- Anticarcinogenic Agents / pharmacology*
- Apoptosis / drug effects*
- Camellia sinensis
- Catechin / analogs & derivatives*
- Catechin / pharmacology
- Cell Proliferation / drug effects*
- Cyclin-Dependent Kinase 4 / metabolism
- Dose-Response Relationship, Drug
- Female
- Humans
- Leiomyoma / metabolism
- Leiomyoma / pathology*
- Plant Extracts / pharmacology
- Proliferating Cell Nuclear Antigen / metabolism
- Proto-Oncogene Proteins c-bcl-2 / metabolism
- Signal Transduction / drug effects
- Tea
- Time Factors
- Tumor Cells, Cultured
- Uterine Neoplasms / metabolism
- Uterine Neoplasms / pathology*
- bcl-2-Associated X Protein / metabolism
- Anticarcinogenic Agents
- Plant Extracts
- Proliferating Cell Nuclear Antigen
- Proto-Oncogene Proteins c-bcl-2
- Tea
- bcl-2-Associated X Protein
- Catechin
- epigallocatechin gallate
- Cyclin-Dependent Kinase 4
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Source: PubMed