Abstract
Physiological concentrations of the green tea extract epigallocatechin-3-gallate (EGCG) caused growth inhibition in estrogen receptor α (ERα)-positive MCF7 cells that was associated with down-regulation of the ERα 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 ERα-positive cell line T47D that possesses mutant p53. EGCG increased ERα protein levels and as a consequence, the cells responded significantly better to an ERα antagonist tamoxifen (TAM) in the presence of EGCG. EGCG significantly increased cell death in an ERα-negative cell line, MDA-MB-231 that also possesses mutant p53. EGCG significantly increased the ERα 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 (αIR3). 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.
Highlights
Tea originated from China and has been produced and consumed for thousands of years
We aimed to assess if physiological concentrations of EGCG affected cell growth, cell death, and altered key molecules [insulin-like growth factor-1 receptor (IGF-1R), ER, and HER2] that have been implicated in regulating these processes and if such changes influenced the sensitivity to agents targeting breast cancer cells
EGCG AT PHYSIOLOGICAL CONCENTRATIONS INHIBITED CELL PROLIFERATION AND INCREASED CELL DEATH OF BREAST CANCER CELLS It has been reported that physiological, achievable serum concentration of EGCG is not higher than 1 μM [22,23,24] or up to 7 μM with a supplement [25]. To analyze whether these physiological levels of EGCG have any impact on breast cancer cell proliferation, we assessed doses of EGCG up to 1 μM in estrogen receptor α (ERα)-positive breast cancer cell lines, MCF7 (Figure 1A), T47D (Figure 1B), and an ERα-negative cell line MDA-MB-231 (Figure 1C)
Summary
Tea originated from China and has been produced and consumed for thousands of years. Tea is the most widely consumed beverage next to water and provides a source of the well-known polyphenols, which are associated with a reduction in cancer risk [1]. After steaming or pan-frying, enzymes are inactivated to prevent the oxidation of tea polyphenols, which are called catechins. There are four major catechins in green tea: (−)-epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), (−)-epicatechin gallate (ECG), and (−)-epicatechin (EC) [2]. EGCG is the most abundant and biologically active polyphenolic catechin in green tea, and exerts multiple effects in humans. While the cancer preventive effects of green tea have been well established in animal models, its activity in humans is still controversial [4]
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