The regulation of steroid receptors by epigallocatechin-3-gallate in breast cancer cells

Abstract

It has been reported that phytoestrogen epigallocatechin gallate (EGCG) suppresses cancer cell proliferation and may have antitumor properties. In this study, we analyzed the effects of EGCG on estrogen receptor α (ERα) and progesterone receptor in hormone-dependent T-47D breast cancer cells. Western blot analysis revealed EGCG induced a concentration-dependent decrease in ERα protein levels, with a 56% reduction occurring with 60 µM EGCG when compared to controls. Downregulation of ERα protein levels was observed after 24-hour co-treatment of T-47D cells with 60 µM EGCG and 10 nM 17β-estradiol (E2). The proliferative effect of E2 on cell viability was reversed when treated in combination with EGCG. In contrast, the combination of EGCG with the pure ER antagonist, ICI 182, 780, showed no further reduction in cell number as only 5% of the cells were viable after 6 days of treatment. These studies may provide further understanding of the interactions among flavonoids and steroid receptors in breast cancer cells.

Effects of green tea, matcha tea and their components epigallocatechin gallate and quercetin on MCF‑7 and MDA-MB-231 breast carcinoma cells

“…It was demonstrated in various studies that EGCG and quercetin exhibit anticancer activity. Besides steroid receptor (9) and PPARγ receptor (10) interaction, other assumed mechanisms of action include interaction with the PI3K/Akt/mTOR signaling pathway (11), VEGF (12), the the 67-kDa laminin receptor (67-LR) (13), p53, Bax protein (14) and Bcl-2 (15).…”

Co-Adjuvant Therapy Efficacy of Catechin and Procyanidin B2 with Docetaxel on Hormone-Related Cancers In Vitro

“…Such a difference could be related to the molecular characteristics of cells as well as the compounds characteristics, particularly variation in the cell ability to deal with estrogen, progesterone and androgen activities modulated by the compounds tested (Figure 12). It is postulated that some types of CATs have binding affinity for ERβ, ERα, PR and/or AR and could exhibit similar effects to that of selective modulators of hormone receptors, such as ER modulators (SERMs) [66][67][68][69][70], selective estrogen down-regulators (SERDs) [71][72][73], selective progesterone receptors modulators (SPRMs) [72] and selective androgen receptor modulators (SARMs), even in androgen-independent PC [74,75]. Furthermore, it is suggested that CATs can inhibit different enzymes involved in estrogen and androgen synthesis such as aromatase (aromatase inhibitors (AIs)] [76][77][78][79]) and 5α-reductase [80,81].…”

“…Additionally, it is suggested that some CATs act as ER down-regulators [71][72][73], particularly through ERα36 in TNBC progenitor cells [84]. In addition, it is suggested that some CATs can indirectly down-regulate ERα [73] via PR [72] in MCF-7 cells.…”

“…5α-reductase inhibitors block 5α-DTH production. CATs, by acting on hormonal receptors, could have pharmacological actions similar to those of modulators of these receptors (SERMs, SERDs, SPRMs, SARMs)[66][67][68][69][70][71][72][73][74][75]82]. In addition, they would act by inhibiting aromatase[76][77][78][79] or 5-α reductase[81].…”

Polyphenols as Promising Drugs against Main Breast Cancer Signatures

“…Conversely, high concentrations promote processes such as apoptosis or cell cycle blockage resulting in antitumor effects as mentioned above. In addition, ER expression is also regulated by some polyphenols, for example, EGCG, which downregulates ER-α protein, mRNA and gene promoter activity in MCF-7 [ 198 ] and ER and PR in T-47D [ 199 ] cell lines. There are so many additional examples of flavonoids, like apigenin, luteolin myricetin, anthocyanidins or quercetin, and other compounds, such as stilbenes, ellagitannins, sulforaphanes, curcuminoids and tocopherols, among others, that are extensively reviewed [ 197 , 200 ].…”