Metformin and Metronidazole as Combined Therapeutic Agents in Cervical Cancer: Modulation of Hsp60 and Hsp70 Chaperonins | ||||
| Journal of Bioscience and Applied Research | ||||
| Articles in Press, Accepted Manuscript, Available Online from 02 August 2025 | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/jbaar.2025.380860.1196 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Youssef Shakuri Yasin   1; Kawakeb N Abdulla 2; Aqeela Hayder Majeed 3; Nora Sabah Rasoul 4; Azal Hamoody Jumaa 2
| ||||
| 1Bilad Alrafidain University College | ||||
| 2Iraqi National Cancer Research Center/University of Baghdad, Baghdad, Iraq | ||||
| 3College of Medicine -University of Karbala, Karbala, Iraq | ||||
| 4College of Medicine - University of Karbala, Karbala, Iraq | ||||
| Abstract | ||||
| Objective: Our study aimed to investigate the anticancer effects of a metformin-metronidazole mixture on the HeLa cell line and evaluate its potential to target Hsp70 and Hsp60. Methods: over 24 and 72 hours of incubation, the HeLa cancer cell line and human fibroblast cell line were utilized to assess the cytotoxicity and selective toxicity of the mixture on cervical cancer proliferation, using cisplatin as a positive control. The concentrations of metformin, metronidazole, the mixture, and cisplatin ranged from 0.1 to 1,000 µg/ml. The combination index (CI) and selective toxicity index (SI) values were calculated to identify the synergistic behavior of the mixture's components and its selectivity for cancer cells. Furthermore, computational molecular docking simulations were conducted to evaluate the affinity of metformin and metronidazole for binding to heat shock proteins 70 and 60. Results: The cytotoxicity assay and SI results indicated that the mixture selectively inhibits cervical cancer growth, with a pattern dependent on concentration and incubation time, while exhibiting a reduced effect on the viability of the HFF cell line. The CI analysis revealed that the interaction between metformin and metronidazole showed a synergistic pattern, particularly after 72 hours of incubation. The computational molecular docking simulations demonstrated that metformin and metronidazole target Hsp70 and Hsp60 with docking scores of -6.2 kcal/mol and -6.7 kcal/mol, respectively. Conclusion: The findings from the study's MTT assay, SI, CI, and computational docking simulations suggest that the mixture offers a promising therapeutic option for cervical cancer, considering their established adverse effects and pharmacokinetic profiles. | ||||
| Keywords | ||||
| : Combination index; HeLa Cells; Metformin; Metronidazole; Molecular Docking Simulation | ||||
|
Statistics Article View: 40 |
||||
