Combination of EGCG and BH3 Mimetic Inhibitor Enhances Apoptosis of MCF-7 and MDA-MB-231 Cancer Cells

Elevated levels of myeloid cell leukemia 1 (Mcl-1) have been shown to counteract the proapoptotic effects of ABT-737, thereby promoting cell survival and contributing to treatment resistance in tumors. This study aimed to evaluate the effect of epigallocatechin gallate (EGCG) on the expression of Mcl-1 and the sensitivity of MDA-MB-231 and MCF-7 breast cancer cells to ABT-737.

Cell toxicity was assessed through the implementation of the MTT assay. To evaluate the impact of treatments on cell proliferation, both the cell growth assay and the colony formation assay were employed. The mRNA levels of Mcl-1 and matrix metalloproteinase 2 (MMP-2) were measured using quantitative real-time reverse transcription polymerase chain reaction. In order to assess cell migration, the wound healing assay was utilized. The presence of apoptosis was detected through various methods, including ELISA cell death assay, caspase-3 activity assay, and Hoechst 33342 staining.

Combined EGCG and ABT-737 significantly reduced IC₅₀ values and suppressed colony formation, migration, and survival in MCF-7 and MDA-MB-231 breast cancer cells more effectively than either agent alone. EGCG downregulated Mcl-1 and MMP-2 mRNA expression. Critically, EGCG-mediated Mcl-1 suppression enhanced ABT-737-induced apoptosis. This synergy highlights EGCG's role in overcoming ABT-737 resistance via Mcl-1 inhibition.

EGCG has been shown to possess antitumor properties in breast cancer cells. Moreover, EGCG has the potential to enhance the apoptotic effects of ABT-737 by suppressing the expression of Mcl-1.