Abstract
The role of EGCG, a major green tea catechin in breast cancer therapy is poorly understood. The present study tests the hypothesis that EGCG can inhibit the activation of HIF-1α and NFκB, and VEGF expression, thereby suppressing tumor angiogenesis and breast cancer progression. Sixteen eight-wk-old female mice (C57BL/6 J) were inoculated with 10^6 E0771 (mouse breast cancer) cells in the left fourth mammary gland fat pad. Eight mice received EGCG at 50–100 mg/kg/d in drinking water for 4 weeks. 8 control mice received drinking water only. Tumor size was monitored using dial calipers. At the end of the experiment, blood samples, tumors, heart and limb muscles were collected for measuring VEGF expression using ELISA and capillary density (CD) using CD31 immunohistochemistry. EGCG treatment significantly reduced tumor weight over the control (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01), tumor CD (109 ± 20 vs. 156 ± 12 capillary #/mm^2; P < 0.01), tumor VEGF expression (45.72 ± 1.4 vs. 59.03 ± 3.8 pg/mg; P < 0.01), respectively. But, it has no effects on the body weight, heart weight, angiogenesis and VEGF expression in the heart and skeletal muscle of mice. EGCG at 50 μg/ml significantly inhibited the activation of HIF-1α and NFκB as well as VEGF expression in cultured E0771 cells, compared to the control, respectively. These findings support the hypothesis that EGCG, a major green tea catechin, directly targets both tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of breast cancer, which is mediated by the inhibition of HIF-1α and NFκB activation as well as VEGF expression.
Highlights
The term ‘green tea’ refers to the product manufactured from fresh tea leaves by steaming or drying at elevated temperatures with the precaution to avoid oxidation of the polyphenolic components known as catechins [ 1]
Hypoxia causes the activation of HIF-1, in which it stimulates vascular endothelial growth factor (VEGF) expression
We hypothesizes that EGCG directly targets both of tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of breast cancer, which is mediated by the inhibition of HIF-1α and NFκB activation as well as VEGF expression
Summary
The term ‘green tea’ refers to the product manufactured from fresh tea leaves by steaming or drying at elevated temperatures with the precaution to avoid oxidation of the polyphenolic components known as catechins [ 1]. The natural product (−)epigallocatechin-3-gallate (EGCG) accounts for 50-80% of catechins in green tea, representing 200–300 mg in a brewed cup of green tea [ 2]. Several other catechins such as (−)-epicatechin-3-gallate (ECG), (−)-epigallocatechin (EGC), and (−)epicatechin (EC) are found in lower abundance in green tea [ 3]. EGCG is defined as a major green tea catechin that contributes to beneficial therapeutic effects, including anti-oxidant, anti-inflammatory, anti-cancer, and immunomodulatory effects [ 4– 6]. Studies conducted on cell-culture systems and animal models as well as human epidemiological studies show that EGCG in green tea could afford protection against a variety of cancer types [ 7]. The investigations of green tea or EGCG in breast cancer using animal model are very limited, and the role of EGCG in breast cancer therapy is poorly understood
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