Combined treatment with doxorubicin and Zm-093 reduced Bcl-2 expression by 57% and increased caspase-3 expression 5.7-fold in MCF-7 breast cancer cells compared to control.
Does the combination of doxorubicin and Zm-093 enhance apoptosis in MCF-7 breast cancer cells?
The combination of doxorubicin and the novel sulfonamide Zm-093 synergistically enhances apoptosis in MCF-7 breast cancer cells.
Introduction: Breast cancer (BC) is a major global health issue. Combination therapies using chemical compounds have shown potential benefits, including reduced toxicity, slowed cancer cell growth, and improved treatment outcomes, compared to single-drug treatments. Objectives: This study investigates the synergistic effects of doxorubicin (DOX) and Zm-093, a novel sulfonamide derivative with unique properties that offer potential advantages over existing sulfonamide compounds, including enhanced solubility and improved bioavailability, on apoptosis induction in BC cell lines. Methods: Zm-093 was synthesized, and its structure was confirmed through Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy. Cell viability was assessed using the MTT assay, while the combination index (CI) was calculated with Compusyn software to evaluate the synergistic interaction between DOX and Zm-093 in MCF-7 cells. The apoptotic effects of these compounds were further analyzed using western blotting, flow cytometry, and TUNEL assays. Results: Notably, the combined treatment of DOX and Zm-093 at concentrations of 0.36 µM and 14.5 µM resulted in a 57% reduction in Bcl-2 expression compared to the control group. In contrast, expressions of pro-apoptotic proteins Bax and tBid, as well as caspase-3, increased significantly by 2.4, 3.3, and 5.7 times, respectively. Flow cytometry and TUNEL assay results indicated that the combination therapy significantly enhanced early apoptosis while minimizing necrosis. Conclusion: These findings confirm that DOX and Zm-093 exhibit synergistic effects on apoptotic pathways in MCF-7 cells, highlighting the potential of Zm-093 as a novel therapeutic agent with improved efficacy and reduced toxicity compared to existing sulfonamide compounds.
Pedarpour et al. (2026) studied Breast cancer. Doxorubicin and Zm-093 combination vs. Control group was evaluated on Apoptosis induction and protein expression (Bcl-2, Bax, tBid, caspase-3). Combined treatment with doxorubicin and Zm-093 reduced Bcl-2 expression by 57% and increased caspase-3 expression 5.7-fold in MCF-7 breast cancer cells compared to control.