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Antiproliferative and proapoptotic effects of epigallocatechin gallate on human leiomyoma cells

Antiproliferative and proapoptotic effects of epigallocatechin gallate on human leiomyoma cells

Fertil Steril. 2010 Oct;94(5):1887-93. doi: 10.1016/j.fertnstert.2009.08.065. Epub 2009 Oct 12.

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 μみゅーM of EGCG compared with untreated control. Gene expression profiling indicated that EGCG treatment up-regulated representative genes from the transforming growth factor βべーた (TGF-βべーた) and stress pathways, while inhibiting the survival pathway and NFκかっぱB-dependent inflammatory pathway. Western blot analysis confirmed that EGCG at ≥50 μみゅーM 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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

Substances

  • 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