Effects of Physiological Levels of the Green Tea Extract Epigallocatechin-3-Gallate on Breast Cancer Cells

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.

Caffeine and Caffeic Acid Inhibit Growth and Modify Estrogen Receptor and Insulin-like Growth Factor I Receptor Levels in Human Breast Cancer

“…Coffee beans are one of the richest dietary sources of the antioxidants caffeine and the plant phenolic compound caffeic acid, both of which may be mechanistically involved in the cancersuppressive properties of coffee. Various dietary and lifestyle factors are also known to influence the sensitivity to cancer treatment (10,16). In line with this, our group recently showed in a subset of the present study cohort, that moderate to high coffee consumption was associated with improved disease-free survival among ER þ tamoxifen-treated women (17).…”

“…In recent years, mechanisms involved in mediating cancer chemopreventive effects of naturally derived plant polyphenols from green tea and coffee have been widely studied in several neoplasias, including breast and prostate cancer (10)(11)(12)(13). However, there have been few translational studies on anticancer effects of coffee in relation to ER status in breast cancer.…”

Complementary/Alternative Medicine Strategies for Prevention and or Cure of Breast Cancer: A Review

“…It also caused increased cell death of another breast cancer cell line, MDA MB-231 which is estrogen receptor negative. Further it has been shown to increase sensitivity to tamoxifen treatment [23]. Wang et al showed that EGCG potentiates the effect of curcumin in causing growth inhibition and inducing apoptosis of MCF 7 breast cancer cells.…”

Epigallocatechin 3-gallate applications on HT-29 and MCF-7 cell lines andevaluation of tumor suppressor gene methylation

“…EGCG is the major component of catechins found in green tea and exists in four active forms: (1)-epigallocatechin-3-gallate (EGCG), (2)-epigallocatechin (EGC), (3)-epicatechin-3-gallate (ECG), and (4)-epicatechin (EC) (Zeng et al, 2014). Catechins, which are polyphenols, constitute nearly 30%-40% of the dry weight of green tea (Lecumberri et al, 2013;Zeng et al, 2014), which is one of the most popular beverages in the world, after water.…”

“…Catechins, which are polyphenols, constitute nearly 30%-40% of the dry weight of green tea (Lecumberri et al, 2013;Zeng et al, 2014), which is one of the most popular beverages in the world, after water. EGCG is an important compound, as it has antitumor activity.…”