Differential Effects of EGCG, a Green Tea Antioxidant, on Vascular Endothelial Growth Factor (VEGF) Expression and Proliferation in Cultured ER‐positive and ER‐negative Human Breast Cancer Cells

Abstract

Estrogen receptor (ER)‐positive breast cancers have a better prognosis than ER‐negative breast cancers, which are more aggressive. The present study determines whether EGCG, a green tea antioxidant, exerts different effects on VEGF expression and proliferation in cultured ER‐positive (MCF‐7) and ER‐negative (MDA‐MB‐231) human breast cancer cells. MCF‐7 and MDA‐MB‐231 cells were cultured using RPMI 1640 media with 10% FBS. ELISA showed that VEGF and VEGF receptor‐2 were more highly expressed in ER‐negative cells than ER‐positive cells (>8‐fold, P<0.01; n=8). 3H‐thymidine incorporation showed that EGCG at 10, 25, and 50 µg/ml caused a dose‐related inhibition in the proliferation of MCF‐7 cells, by 29, 54, and 85%, compared to the control, respectively (P<0.01). However, the same concentrations of EGCG did not inhibit the proliferation of MDA‐MB‐231 cells. EGCG at 50 µg/ml significantly decreased VEGF expression (1752±49 vs. 2254±91 pg/mg; P<0.01) in cultured MCF‐7 cells, compared to the control. However, EGCG at 10 to 50 µg/ml did not inhibit VEGF expression in cultured MDA‐MB‐231 cells. These results suggest that highly expressed VEGF and its receptor may be involved in the aggressive malignant signaling systems of ER‐negative breast cancers, and that EGCG, a green tea antioxidant, can be used to treat ER‐positive human breast cancers, which are sensitive to EGCG. (HL51971 & AA013821)