Effects of physiological levels of the green tea extract epigallocatechin-3-gallate on breast cancer cells

Physiological concentrations of the green tea extract epigallocatechin-3-gallate (EGCG) caused growth inhibition in estrogen receptor alpha (ER alpha)-positive MCF7 cells that was associated with down-regulation of the ERa and reduced insulin-like growth factor binding protein-2 abundance and increased protein abundance of the tumor suppressor genes p53/p21. In contrast to MCF7 cells that have wt p53, EGCG alone did not change cell proliferation or death significantly in another ER alpha-positive cell line T47D that possesses mutant p53. EGCG increased ER alpha protein levels and as a consequence, the cells responded significantly better to an ER alpha antagonist tamoxifen (TAM) in the presence of EGCG. EGCG significantly increased cell death in an ER alpha-negative cell line, MDA-MB-231 that also possesses mutant p53. EGCG significantly increased the ER alpha and insulin-like growth factor-I receptor levels and thereby enhanced the sensitivities of the cells to TAM and a blocking antibody targeting the insulin-like growth factor-1 receptor (alpha IR3). In contrast to MCF7,T47D and MDA-MB-231 breast cancer cells that exhibited significant changes in key molecules involved in breast growth and survival upon treatment with physiological levels of EGCG, the growth, survival, and levels of these proteins in non-malignant breast epithelial cells, MCF10A cells, were not affected.