Impact of Esomeprazole, Ciprofloxacin and Their Combination on Cervical Cancer Cell Line Proliferation: A Focus on Heat Shock Protein 70 Modulation

Document Type : Research Articles

Authors

1 Department of Gynecology and Obstetrics, College of Medicine, Al-Iraqia University, Iraq.

2 Iraqi National Cancer Research Center/University of Baghdad, Baghdad, Iraq.

3 Bilad Alrafidain University , Iraq.

Abstract

Objective: This investigation aimed to evaluate the combined efficacy of ciprofloxacin and esomeprazole in inhibiting cervical cancer proliferation and their capacity to target heat shock protein 70 in vitro. Methods: The MTT assay was utilized to assess the anticancer properties of the ciprofloxacin-esomeprazole combination on the HeLa cervical cancer cell line. The human fibroblast cell line (HFF) is employed to assess the combination’s safety. The assay was performed within 24 and 72 hours of incubation. Ciprofloxacin, esomeprazole, and their combination concentrations ranged from 0.1 to 1000 µg/ml, with the mixture containing 50% of the individual concentration of each medication when assessed individually. The study employed the selective toxicity index to assess the selectivity of the mixture for cancer cells. The combination index was utilized to evaluate the potential synergistic effects of ciprofloxacin and esomeprazole. This study utilizes computational molecular docking simulations to assess the binding affinity of Ciprofloxacin and esomeprazole to heat shock protein 70 (PDB code: 1hjo). Results: The MTT assay and selective toxicity index results indicated that the combination of ciprofloxacin and esomeprazole selectively inhibited the proliferation of cervical cancer cells. The inhibitory effect depended on the concentration of the mixture and the incubation duration, with a diminished impact on the viability of the HFF cell line. The combination index study indicates that the interaction between ciprofloxacin and esomeprazole shows a synergistic effect at each incubation period. The computational molecular docking simulation indicated that ciprofloxacin and esomeprazole target Hsp 70, with docking scores of -7.4 kcal/mol and -7.3 kcal/mol, respectively. Conclusion: Our findings from the MTT assay, selective toxicity index, combination index, and computational docking simulations suggest that the combination of ciprofloxacin and esomeprazole is a promising option for treating cervical cancer, given their set adverse effects and pharmacokinetic profiles.

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