A dual-targeted attack: 2-benzofuran chalcone–tamoxifen combination induces apoptosis and suppresses metastatic behavior in ER+ breast cancer
Year: 2025
Type: article
Abstract: In this study, we investigated the anticancer effects of two synthesized 2-benzofuran-substituted chalcone derivatives (2a-2b) in combination with tamoxifen on MCF-7 estrogen receptor-positive (ER+) breast cancer cells. Cytotoxicity was evaluated using the sulforhodamine B (SRB) assay in both MCF-7 and non-tumorigenic MCF-10A cells. The combination index (CI) was calculated to determine synergistic interactions. Apoptotic cell death was confirmed via fluorescence microscopy using Annexin-V, Hoechst 33342, and PI staining. The involvement of apoptosis, necroptosis, and autophagy was further assessed using Z-VAD-FMK, Necrostatin-1, Necrosulfonamide, and 3-Methyladenine inhibitors. Functional analyses including colony formation, migration, and Matrigel invasion assays were performed. Additionally, gene expression changes in apoptosis, necroptosis, and autophagy-related markers were quantified by qRT-PCR. The combination of 2-benzofuran-chalcone compounds with tamoxifen exhibited a synergistic cytotoxic effect on MCF-7 cells, with significantly lower IC50 values compared to monotherapies, while exerting minimal toxicity on MCF-10A cells. Fluorescence staining revealed increased apoptotic features upon combination treatment. Inhibitor assays confirmed that the cell death mechanism was predominantly caspase-dependent apoptosis, with no significant involvement of necroptosis or autophagy. The combination treatment significantly impaired clonogenic capacity, cell migration, and Matrigel invasion. Gene expression analyses showed upregulation of pro-apoptotic markers and downregulation of anti-apoptotic markers, further validating apoptotic activation. This study demonstrates that 2-benzofuran-substituted chalcone derivatives synergize with TAM to induce apoptosis and suppress proliferative and metastatic potential in ER+ breast cancer cells. These findings highlight the therapeutic promise of 2-benzofuran chalcone–tamoxifen combinations as a novel strategy to enhance anti-tumor efficacy and overcome resistance in hormone-dependent breast cancers.
Source: Results in Chemistry
Institutions: Fırat University, Bursa Uludağ Üni̇versi̇tesi̇
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,870
OpenAlex ID: W4414008552