EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to suppression of cell viability and induction of apoptosis.

Telomerase is elevated in >90% of breast carcinomas and therefore has received much attention as a target for breast cancer therapy and cancer diagnostic research. Dietary components that are capable of inhibiting the growth of cancer cells without affecting the growth of normal cells are receiving considerable attention in developing novel cancer-preventive approaches. Studies have shown that (-)-epigallocatechin-3-gallate (EGCG) from green tea imparts a growth inhibitory effect on cancer cells. Here, we show that treatment of EGCG dose-dependently inhibited (20-100%) the reproductive or colony forming potential, and also decreased cell viability at different time points studied ( approximately 80% inhibition) in human breast carcinoma MCF-7 cells but had no adverse effect on the growth of normal mammary cells. Treatment of EGCG for 48 and 72 h markedly increased the percentage of apoptotic cells (32-51%) in MCF-7 cells compared to that of non-EGCG treated cells (8-14%). In order to identify the possible mechanism of decreased cell viability and induction of apoptosis in breast carcinoma cells by EGCG, we found that treatment of MCF-7 cells with EGCG dose-dependently inhibited telomerase activity (40-55%), and also inhibited the mRNA expression (40-55%) of hTERT, a catalytic subunit of telomerase. Additional studies demonstrated that EGCG also inhibited the protein expression of hTERT, which indicated that inhibition of telomerase was associated with down-regulation of hTERT. Together, our results indicate that EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to the suppression of cell viability and induction of apoptosis, thus providing the molecular basis for the development of EGCG as a novel chemopreventive and pharmacologically safe agent against breast cancer.