The green tea compound, (−)‐epigallocatechin‐3‐gallate downregulates N‐cadherin and suppresses migration of bladder carcinoma cells
- 8 March 2007
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 102 (2), 377-388
- https://doi.org/10.1002/jcb.21299
Abstract
Green tea has been reported as potential dietary protection against numerous cancers and has been shown to have activity in bladder tumor inhibition in different animal models. The goal of this study was to examine the effects of (−)‐epigallocatechin gallate (EGCG—the major phytochemical in green tea) on growth inhibition and behavior of human bladder carcinoma cells and to identify the altered signaling pathway(s) underlying the response to EGCG exposure. EGCG inhibited the in vitro growth of invasive bladder carcinoma cells with an IC50 range of 70–87 µM. At a concentration of 20 µM, EGCG decreased the migratory potential of bladder carcinoma cells with concomitant activation of p42/44 MAPK and STAT3 and inactivation of Akt. Using biochemical inhibitors of MAPK/ERK, and siRNA to knockdown STAT3 and Akt, inhibition of migration was recorded associated with Akt but not MAPK/ERK or STAT3 signaling in bladder cells. In addition, EGCG downregulated N‐cadherin in a dose‐dependent manner where reduction in N‐cadherin expression paralleled declining migratory potential. Continuous feeding of EGCG to mice prior to and during the establishment of bladder carcinoma xenografts in vivo revealed >50% reduction in mean final tumor volume (P ≤ 0.05) with no detectable toxicity. EGCG inhibited bladder carcinoma cell growth and suppressed the in vitro migration capacity of cells via downregulation of N‐cadherin and inactivation of Akt signaling. Continuous administration of EGCG to mice revealed significant inhibition of tumor growth in vivo indicating a possible preventative role for green tea in bladder cancer. J. Cell. Biochem. 102: 377–388, 2007.Keywords
This publication has 44 references indexed in Scilit:
- Chemoprevention of Human Prostate Cancer by Oral Administration of Green Tea Catechins in Volunteers with High-Grade Prostate Intraepithelial Neoplasia: A Preliminary Report from a One-Year Proof-of-Principle StudyCancer Research, 2006
- Lysosomal trafficking of β-catenin induced by the tea polyphenol epigallocatechin-3-gallateMutation Research, 2005
- Growth Inhibitory and Antimetastatic Effect of Green Tea Polyphenols on Metastasis-Specific Mouse Mammary Carcinoma 4T1 Cells In vitro and In vivo SystemsClinical Cancer Research, 2005
- Histone deacetylase inhibitors upregulate plakoglobin expression in bladder carcinoma cells and display antineoplastic activity in vitro and in vivoInternational Journal of Cancer, 2004
- Oral Consumption of Green Tea Polyphenols Inhibits Insulin-Like Growth Factor-I–Induced Signaling in an Autochthonous Mouse Model of Prostate CancerCancer Research, 2004
- Growth inhibition and cell cycle arrest effects of epigallocatechin gallate in the NBT‐II bladder tumour cell lineBJU International, 2004
- Inhibition of β-catenin/Tcf activity by white tea, green tea, and epigallocatechin-3-gallate (EGCG): minor contribution of H2O2 at physiologically relevant EGCG concentrationsBiochemical and Biophysical Research Communications, 2002
- Cell Cycle Dysregulation by Green Tea Polyphenol Epigallocatechin-3-GallateBiochemical and Biophysical Research Communications, 2000
- The role of STATs in transcriptional control and their impact on cellular functionOncogene, 2000
- Influence of Drinking Green Tea on Breast Cancer Malignancy among Japanese PatientsJapanese Journal of Cancer Research, 1998