In-vitro investigation of anticancer activity of 2-bromo-n-(4-sulfamoyl phenyl) propane amide in combination with different chemotherapeutic drugs

Breast cancer is a prevalent and potentially life-threatening disease that affects women globally. The diversity of breast cancer subtypes contributes to variations in disease progression, treatment response, and metastasis risk factors. Carbonic anhydrase IX (CA IX) is an enzyme that plays a significant role in regulating pH levels in cancer cells, including breast cancer. It is known to be highly expressed in various tumor types, including breast cancer, and is believed to play a role in cancer cell survival, invasion, and metastasis promotion. Targeting CA IX has emerged as a promising therapeutic strategy to disrupt vital functions of cancer cells and potentially hinder tumor progression. The aim of this study was to evaluate the therapeutic potential of the newly synthesized sulfonamide derivative MMH-1 in breast cancer cells and its combination with chemotherapy drugs. The study focused on understanding the cytotoxic and apoptotic effects of MMH-1 on cancer cells, investigating its binding ability to carbonic anhydrase IX (CA IX), and exploring its synergistic effects with other chemotherapy drugs. Breast cancer cells (4T1) were cultured and treated with MMH-1, Epirubicin, and their combinations. Cell viability analyses, morphological staining, flow cytometry analysis, cell cycle analysis, measurement of reactive oxygen species (ROS) levels, and mitochondrial membrane potential analysis were performed to assess the effects of the treatments. Statistical analyses demonstrated that MMH-1 exhibited significant cytotoxic effects, leading to decreased cell viability and morphological changes in breast cancer cells. Furthermore, when used in combination with other chemotherapy drugs, MMH-1 showed significant cytotoxic effects on breast cancer cells. The conducted study revealed the potential binding ability of MMH-1 to CA IX, as evidenced by molecular docking analysis, indicating its potential to disrupt the enzyme's function. Additionally, the combination treatment of MMH-1 with Epirubicin resulted in enhanced cytotoxicity, with further decrease in cell viability and increased apoptotic cell population. Moreover, the combination treatment led to cell cycle arrest, mitochondrial dysfunction, and increased oxidative stress in breast cancer cells. These findings underscore the therapeutic potential of MMH-1 in breast cancer treatment. The combination therapy of MMH-1 with Epirubicin exhibited improved efficacy and synergistic effects. These findings support the development of MMH-1 and combination therapies to enhance breast cancer treatment outcomes.