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cDNA microarray analysis of endothelial cells in response to green tea reveals a suppressive phenotype
Maryam R Sartippour1, David Heber, Susanne Henning
1Division of Oncology, Department of Surgery, University of California, Los Angeles, CA 90095-1782, USA.
Abstract:
Green tea may prevent cancer, partially by inhibiting tumor angiogenesis. Our previous studies showed that green tea extract was effective in inhibiting breast cancer and endothelial cell proliferation in vitro, and suppressed xenograft size and decreased the tumor vessel density in vivo. Here, we set out to further investigate the molecular mechanisms of this observed angiogenesis suppression. We utilized cDNA microarray technology to profile the global changes in endothelial cellular gene expression in response to green tea. HUVEC (human umbilical vein endothelial cells) were exposed in vitro to green tea for either 6 or 48 h. Only statistically significantly differentially expressed genes were analyzed. Gene profiling demonstrated a global down-regulation of multiple genes involved in endothelial cell growth, signal transduction and oxidation, accompanied by up-regulation of several apoptotic genes. We validated these observations by showing positive correlations with biological assays of cellular proliferation, cell cycle, and apoptosis. The anti-oxidant characteristics of green tea and its metabolites were confirmed in the ORAC (oxygen radical absorbance capacity) assay. cDNA microarray revealed that green tea has an overall suppressive effect on multiple pathways in endothelial cells. This study contributes to the comprehensive analysis of the molecular effects of green tea on endothelial cells, and provides insight into genes that may be important in chemoprevention.
Insights
Green tea extract suppresses tumor growth by inhibiting blood vessel formation in endothelial cells. This study reveals molecular mechanisms, identifying key genes for cancer chemoprevention.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Green tea consumption is linked to cancer chemoprevention.
- Green tea extract inhibits cancer cell proliferation and angiogenesis.
- Previous studies demonstrated in vitro and in vivo anti-cancer effects of green tea.
Purpose of the Study:
- To investigate the molecular mechanisms of green tea's angiogenesis suppression.
- To identify global gene expression changes in endothelial cells exposed to green tea.
- To understand green tea's role in cancer chemoprevention.
Main Methods:
- Utilized cDNA microarray technology to profile gene expression in human umbilical vein endothelial cells (HUVEC).
- Exposed HUVEC to green tea extract in vitro for 6 and 48 hours.
- Analyzed statistically significant differentially expressed genes and validated findings with biological assays (proliferation, cell cycle, apoptosis) and ORAC assay.
Main Results:
- Green tea down-regulated genes involved in endothelial cell growth, signal transduction, and oxidation.
- Upregulation of several apoptotic genes was observed.
- Confirmed anti-oxidant properties of green tea and its metabolites.
- Demonstrated an overall suppressive effect of green tea on multiple endothelial cell pathways.
Conclusions:
- Green tea exerts a suppressive effect on endothelial cell pathways crucial for angiogenesis.
- Identified specific genes affected by green tea, offering insights into its chemopreventive potential.
- Provides a comprehensive molecular analysis of green tea's anti-angiogenic effects.
