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Induction of apoptosis in human bladder cancer cells by green tea catechins
Brian J Philips1, Christian H Coyle, Shelby N Morrisroe
1Department of Urology, University of Pittsburgh School of Medicine, PA 15213, USA.
Abstract:
Cell culture and animal studies have demonstrated strong chemopreventative effects of green tea and its associated polyphenols in multiple cancers, though the exact mechanisms of action are not well understood. This in vitro study examined the antiproliferative/pro-apoptotic potential of green tea extract (GTE), polyphenon-60 (PP-60), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin-3-gallate (EGCG) in both normal and malignant human bladder cells. Cell growth (proliferation/apoptosis) was measured in UROtsa (normal), SW780 (tumorigenic; low-grade), and TCCSUP (tumorigenic; high-grade) human bladder urothelial cells by cell proliferation (XTT) assay after treatment with 0-80 microg/mL of GTE, PP-60, ECG and EGCG for 72 h. Molecular signaling pathways of catechin-induced apoptosis were analyzed using Human signal transduction RT(2) Profiler PCR array (SuperArray). Compared to control-treated cells, treatment with catechin agents significantly suppressed cell growth in a dose-dependent fashion (P < 0.01), with strongest effects evoked by ECG and EGCG in UROtsa cells, ECG in low-grade RT4 and SW780 cells, and PP-60 and EGCG in high-grade TCCSUP and T24 cells. Microarray analysis indicated distinct differences in mRNA gene expression regarding growth signaling pathway activation induced by EGCG in normal/tumorigenic human bladder cell lines, providing a rationale for the putative therapeutic usage of green tea polyphenols against bladder disease.
Insights
Green tea polyphenols, including EGCG and ECG, show significant antiproliferative and pro-apoptotic effects in normal and malignant human bladder cells. These findings support the potential therapeutic use of green tea extract for bladder cancer prevention.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Green tea polyphenols exhibit chemopreventive properties against various cancers.
- The precise mechanisms underlying green tea's anti-cancer effects are not fully elucidated.
- This study investigates the impact of green tea compounds on human bladder cells.
Purpose of the Study:
- To evaluate the antiproliferative and pro-apoptotic potential of green tea extract (GTE) and its constituents (polyphenon-60, ECG, EGCG) in normal and malignant human bladder cells.
- To analyze the molecular signaling pathways involved in catechin-induced apoptosis.
- To explore the differential effects of these compounds on various grades of human bladder urothelial cells.
Main Methods:
- In vitro study using normal (UROtsa) and malignant (SW780, TCCSUP) human bladder urothelial cell lines.
- Cell proliferation and apoptosis assessed via XTT assay after 72-hour treatment with GTE, PP-60, ECG, and EGCG (0-80 microg/mL).
- Gene expression analysis of molecular signaling pathways using Human Signal Transduction RT2 Profiler PCR Array.
Main Results:
- Catechin treatments significantly suppressed cell growth in a dose-dependent manner (P < 0.01).
- Strongest growth inhibition observed with ECG and EGCG in normal cells, ECG in low-grade tumor cells, and PP-60/EGCG in high-grade tumor cells.
- Microarray analysis revealed distinct gene expression differences in signaling pathways induced by EGCG in normal versus malignant bladder cells.
Conclusions:
- Green tea polyphenols, particularly EGCG and ECG, demonstrate significant antiproliferative and pro-apoptotic effects on human bladder cells.
- Distinct molecular responses to EGCG in normal and malignant cells provide a basis for their therapeutic potential.
- These findings support the use of green tea polyphenols as a chemopreventive strategy against bladder cancer.
