THPM (1,2,3,4‐Tetrahydro pyrimidine) and Berberine Exhibit Synergistic Impact on Inhibition of Cell Migration and Colonization Through ROS‐Mediated Apoptotic Pathways in the Breast Cancer Cells

Abstract Breast cancer is one of the major causes of death in females worldwide. Considering the polypharmacological trend, small molecules like pyrimidine along with berberine, a bioactive anticancer agent may act as effective anticancer drugs having multiple targets with minimal side effects. However, it has never been tested. The present work discloses the efficacy of the combination of 1,2,3,4,‐Tetrahydro pyrimidine (THPM) and Berberine (BBR) in inhibiting cancer progression in human breast cancer cell line, i.e., MCF‐7. THPM were synthesized and characterized, and their anti‐cancerous potential was evaluated by in silico study. The MCF‐7 cells were exposed in vitro with THPM (200 µM), BBR (20 µM/ml) alone or in combination of THPM + BBR (200 µ m + 20 µ m /ml) for 24 h. Intracellular ROS, annexin‐V staining, cell migration, colony formation assay, and gene expression analysis were performed. THPM and BBR both exhibited solid binding affinity against the BCL‐2 protein. Interestingly, co‐treatment of THPM + BBR significantly increased ROS level, annexin‐V positive cells, the expression level of Bax, and Caspase‐3 and inhibited migration and proliferation of MCF‐7 cells. In conclusion, co‐treatment of THPM + BBR exhibits a synergistic impact via inhibiting cell proliferation and inducing ROS‐mediated apoptosis in MCF‐7 cells suggesting that THPM and BBR could be used as novel therapeutic agents against breast cancer.