Investigation of the anti-cancer effect of MMH-1 in the 4T1 breast cancer mouse model

Investigation of the Anti-Cancer Effect of MMH-1 in the 4T1 Breast Cancer Mouse Model Aim: CA IX enzyme has supportive roles in the growth, development, survival, invasion and metastasis of cancer cells. Sulfonamides have an inhibitory effect on this enzyme and may contribute to cancer treatment. In this study, we aimed to explain the effect of MMH-1, a sulfonamide derivative, on breast cancer both in vitro and in vivo, in cytotoxic, metabolic and molecular levels. Material and Method: After examining the inhibitory effect of MMH-1 on CA IX with Molecular Docking, in vitro part of the study was started. The cytotoxic effects of MMH-1 on 4T1 cells were determined by the MTT. Apoptotic effects were analyzed by AO/EtBr staining and Annexin-V. In the in vivo part, both protein and gene expressions of CA IX, Vimentin, E-Cadherin and Caspase 3 in tumor tissues were analyzed and histopathological examination was performed. Also, metabolomic analysis was performed with blood samples. Results: Molecular Docking results showed that MMH-1 has binding affinity and modes with CA IX. It was observed that MMH-1 triggered apoptosis in vitro and in vivo. Histopathological results also supported that MMH-1 was effective in the reduction of tumor volumes and the death of cancer cells. It also showed successful results in reducing the metabolomic changes caused by cancer. Conclusion: These findigs showed that MMH-1 has an inhibitory effect on CA IX and kills cancer cells by triggering apoptosis. Different doses of MMH-1 and its combined use with different chemotherapeutic agents can be used as potential therapeutic candidate in the treatment of breast cancer. Keywords: Apoptosis, Breast Cancer, Cancer Model, MMH-1, Sulfonamide