Scrutiny of the Co-Cytotoxic Impact of Metformin-Omeprazole on the Cervical Cancer Cell Line and Their Aptitude to Target Heat Shock 60

Khudhur, Rasha Kareem; Yahiya, Yahiya Ibrahim; Majeed, Aqeela Hayder; Yasin, Youssef Shakuri; Jumaa, Azal Hamoody

doi:10.31557/APJCP.2025.26.4.1353

Scrutiny of the Co-Cytotoxic Impact of Metformin-Omeprazole on the Cervical Cancer Cell Line and Their Aptitude to Target Heat Shock 60

Document Type : Research Articles

Authors

¹ Pharmacology Department, College of Medicine, University of Misan, Iraq.

² Department of Pharmacology, Faculty of Pharmacy, University of Alkafeel, Najaf, Iraq.

³ College of Medicine, University of Karbala, Karbala, Iraq.

⁴ Bilad Alrafidain University, Diyala, 32001, Iraq.

⁵ Iraqi National Cancer Research Center, University of Baghdad, Baghdad, Iraq.

10.31557/APJCP.2025.26.4.1353

Abstract

Objective: This study aimed to assess the simultaneous effect of the metformin–omeprazole combination on inhibiting cervical cancer proliferation. Their ability to target heat shock protein 60. Methods: The anticancer properties of the metformin–omeprazole combination in cancer treatment were evaluated by employing a cervical cancer cell line (HeLa cell line). The assessment included two incubation periods: one of 24 hours and another of 72 hours. The concentrations of metformin, omeprazole, and their combination varied from 0.1 to 1000 µg/ml. The study encompassed an estimated combination index value to assess the potential synergistic effect of metronidazole and linagliptin. The study employs computational molecular docking simulation to determine the affinity of metformin and omeprazole for binding with heat shock protein 60. Results: The study concluded that the metformin-omeprazole combination significantly reduced the proliferation of cervical cancer cells. The inhibitory effect was demonstrated to depend on the mixture’s concentration and the treatment duration. The combination index indicates that metformin and omeprazole synergistically interacted. furthermore, the computational molecular docking simulation indicated that metformin and omeprazole exhibited a propensity to associate with Hsp 60. The docking scores for metformin and omeprazole were measured at -7.3 kcal/mol and -6.2 kcal/mol, respectively. Conclusion: Study indicates that the simultaneous use of metformin and omeprazole synergistically suppresses the growth of cervical cancer cells via both cell cycle-specific and cell cycle-nonspecific pathways. The findings, corroborated by molecular docking studies, demonstrated that metformin and omeprazole can bind to Heat Shock Protein 60. Furthermore, the molecular docking data elucidate the synergistic interactions among the combination components since every drug occupies a distinct binding site on Hsp 60, indicating a complementary binding mode with Hsp 60. Regarding the expected adverse impact and the known pharmacokinetic profile of the mixture’s components, the mixture offered an attractive alternative treatment for cervical cancer.

Keywords