Antiproliferative and proapoptotic effects of epigallocatechin gallate on human leiomyoma cells.
OBJECTIVE
To investigate the effects of epigallocatechin gallate (EGCG), an extract of green tea on cultured human leiomyoma cells (HuLM).


METHODS
Laboratory study.


METHODS
University hospitals.


METHODS
Not applicable.


METHODS
Not applicable.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Zhang
Dong
D
Department of Obstetrics and Gynecology, Center for Women's Health Research, Meharry Medical College, Nashville, Tennessee 37208, USA.
Al-Hendy
Mohamed
M
Richard-Davis
Gloria
G
Montgomery-Rice
Valerie
V
Rajaratnam
Veera
V
Al-Hendy
Ayman
A
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D028241:Camellia sinensis; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016588:Anticarcinogenic Agents; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D013662:Tea; D051028:bcl-2-Associated X Protein; D002392:Catechin; C045651:epigallocatechin gallate; D051358:Cyclin-Dependent Kinase 4