Potential mechanisms for the synergistic cytotoxicity elicited by 4-hydroxytamoxifen and epigallocatechin gallate in MDA-MB-231 cells

Abstract

Potential mechanisms for the synergistic cytotoxicity elicited by epigallocatechin gallate (EGCG) (25 μM) and 4hydroxytamoxifen (4-OHT) (1 μM) in MDA-MB-231 human breast cancer cells were investigated. The role of apoptosis was determined using chromatin condensation and Annexin-V staining. Condensed chromatin was visible following 24 h of combination treatment while flow cytometry experiments demonstrated that apoptosis was 2-fold greater following 36 h of combination treatment compared to EGCG. The temporal appearance of cells in G 1 -arrest did not correlate with apoptosis and thus was not considered to be a viable mechanism for the enhancement of apoptosis. While 4-OHT was a weak competitive inhibitor of microsomal UGT activity (K i 95 μM), it did not alter the metabolism of EGCG as the rate of disappearance of EGCG from the media was the same for cells treated with either EGCG or EGCG + 4-OHT. Additionally, the metabolism of EGCG was not shifted toward the production of active methylated metabolites, as neither 4' were cytotoxic toward MDA-MB-231 cells. In conclusion, the synergistic cytotoxicity elicited by the combination of EGCG and 4-OHT results from an earlier induction of apoptosis but this was not caused by an increase in G 1 -arrest or 4-OHT-mediated changes in the metabolism of EGCG.

The combination of epigallocatechin gallate and curcumin suppresses ERα‐breast cancer cell growth in vitro and in vivo

“…For example, combination treatment with EGCG and tamoxifen was synergistically cytotoxic 10 and enhanced apoptosis 40 in MDA-MB-231 human breast cancer cells and decreased tumor growth in a MCF-7 cell xenograft model. 41 Combination treatment of MCF-7 human breast cancer cells with curcumin and genistein also resulted in synergistic growth inhibition, 12 while curcumin and gemcitabine decreased pancreatic tumor volume in an orthotopic model.…”

Interaction of Green Tea Catechins with Breast Cancer Endocrine Treatment: A Systematic Review

“…Stuart et al [8] investigated the role of apoptosis in the synergistic cytotoxicity elicited by 4-OHT (1 μ M ) and EGCG (25 μ M ) in MDA-MB-231 cells. They concluded that the combination of EGCG and 4-OHT results in an earlier and enhanced apoptotic response [8].…”

Mechanisms of anti-cancer effects of plant polyphenols II. Suppression on tumor growth

“…Полифенолы могут также увеличить спектр противоопухолевой активности препарата. Так, использование ЭГКГ совместно с тамоксифеном, который не оказывает действия на клетки рака молочной железы, не несущие эстрогеновых рецепторов, оказалось эффективным в отношении этих клеток in vitro и на модели бестимусных мышей [109,110]. Чрезвычайно важна также способность полифенолов преодолевать часто развивающуюся резистентность раковых клеток к противоопухолевым антибиотикам [111,112].…”