Kawakeb Abdulla

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

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. 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). 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. 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.

Antiproliferative Impact of Linagliptin on the Cervical Cancer Cell Line

This study aimed to assess linagliptin's inhibitory effects on the proliferation of cervical cancer cell lines and investigate its potential for targeting human heat shock protein 90. Linagliptin's cytotoxicity was assessed on a cervical cancer cell line (Hela cancer cell line) at two different incubation periods, 24 and 72 hours. The molecular docking between linagliptin and the receptor protein human Hsp 90 (PDB code: 5XRE) was performed using the Biovia Discovery Studio and AutoDock tool software. The Discovery Studio visualizer generated three-dimensional (3D) and two-dimensional (2D) interactive images. The study's cytotoxicity results demonstrated that linagliptin can inhibit the proliferation of cervical cancer cells. The cytotoxicity exhibited a time-dependent pattern (cell cycle specific). The molecular docking study was conducted to investigate the interaction between linagliptin and human Hsp90. The study identified 11 sites where linagliptin can bind to Hsp90 amino acid residues. The total docking score for this interaction was -10.3 kcal/mol. The most potent binding occurred through conventional hydrogen bonds with the ASP:54 amino acid residues at a distance of 2.93 Å. The docking scores for linagliptin were comparable to those of the reference drug geldanamycin, indicating a strong interaction between linagliptin and Hsp90. The study has found that linagliptin successfully reduces the growth of cervical cancer cells with a time-dependent cytotoxic pattern. The potential anticancer mechanism of linagliptin can be inferred by analyzing the docking score and docking pattern between linagliptin and Hsp90, suggesting that linagliptin targets human Hsp 90.