Exploring the Synergistic Cytotoxicity of Metronidazole and Esomeprazole in Cervical Cancer: Implications for Targeting Hsp90 Chaperone

Objective: This study aimed to evaluate the effect of the metronidazole-Esomeprazole mixture on the inhibition of cervical cancer proliferation and its ability to target heat shock protein 90.Methods: During 24 to 72 hours of incubation, the anticancer effects of metronidazole, esomeprazole, and their mixture were evaluated using the HeLa cervical cancer cell line. In contrast, the human fibroblast cell line (HFF) was used to assess the safety of the mixture. The concentrations of metronidazole, esomeprazole, and the mixture ranged from 0.1 to 1000 µg/ml. The combination index (CI) and selectivity index (SI) study assessed the potential synergistic effects among the ingredients and mixtures' selective toxicity. Computational molecular docking simulations were utilized to evaluate the binding affinity of metronidazole and esomeprazole with heat shock protein 90. Results: The study's findings indicated that the metronidazole-esomeprazole mixture significantly restricted the proliferation of cervical cancer cells. Simultaneously, it exhibited a reduced impact on the viability of the HFF cell line. The CI and SI scores demonstrate that the interaction between metronidazole and esomeprazole had a synergistic effect, with the mixture selectively killing the cancer cells. Conversely, the computational molecular docking simulation suggested that metronidazole and esomeprazole tended to associate with Hsp90, with docking scores measured at -5 kcal/mol and -9.7 kcal/mol, respectively. Conclusion: The study outcomes of MTT, CI, and SI demonstrated the mixture's ability to inhibit cervical cancer growth selectively. Given the established pharmacokinetics and safety profile of the mixture medication, it presents a promising, effective, and safer option for cervical cancer.