Exploring Omeprazole Effect on Pro-apoptotic Factors in Colorectal Cancer Treatment: Insights from In Silico Studies and Antiproliferative Assessment on HT29 Cells

Abstract

BACKGROUND: Colorectal Cancer (CRC) is one of the most common cancers worldwide. There is an urgent need to identify new drugs for CRC treatment. The apoptotic factors Bad, Bid, Bik, Bim, Bax, and Bak play a crucial role in activating the apoptotic cascade pathways. Inhibition of these factors is a main strategy of cancer therapy. This study investigates the effects of omeprazole on pro-apoptotic factors (Bak, Bad, Bim, Bik, Bid, and Bax) involved in the apoptosis induction in CRC using both in-silico and in-vitro techniques. METHODS: The 3D structure of omeprazole was docked to pro-apoptotic factors obtained from the Protein Data Bank (PDB) using Autodock 4.2.6 software. Molecular Dynamics (MD) simulations were also carried out with GROMACS 2022 to validate the stability of the ligandreceptor complexes. Additionally, an in-vitro experiment was performed to evaluate the cytotoxicity of omeprazole on the HT-29 cell line using the MTT assay. RESULTS: The strong binding affinity between omeprazole and pro-apoptotic factors was observed in molecular docking, with binding energies less than -5.0 kcal/mol. The stability of the omeprazole-receptor complexes was confirmed through MD simulations. Moreover, in vitro results indicated that omeprazole can inhibit the growth and proliferation of colorectal cancer cells with an IC50 value of 400 muM. DISCUSSION: In silico studies presented that omeprazole could affect pro-apoptotic factors responsible for inducing apoptotic pathways. The in vitro studies assume that omeprazole has significant cytotoxic activity against colorectal cancer cell lines. CONCLUSION: These results demonstrated the therapeutic effects of omeprazole by inducing apoptosis in colorectal cancer through the influence of pro-apoptotic factors, and it appears that omeprazole could be a promising drug repurposing candidate for the treatment of colorectal cancer.