Synergistic Cytotoxic Impact of Linagliptin - Ciprofloxacin Combination on Cervical Cancer Cell Line: Insights into Targeting Heat Shock Protein 60

Al-Mahdawi, Tiba Th; Said, Ali Muafaq; Hade, Istikrar M.; Yasin, Youssef Shakuri; Jumaa, Azal Hamoody

doi:10.31557/APJCP.2025.26.6.2117

Synergistic Cytotoxic Impact of Linagliptin - Ciprofloxacin Combination on Cervical Cancer Cell Line: Insights into Targeting Heat Shock Protein 60

Document Type : Research Articles

Authors

¹ Bilad Alrafidain University, College of Pharmacy, Diyala, Iraq.

² Al-Amarah University College, Amarah, Iraq.

³ Iraqi National Cancer Research Center/University of Baghdad, Baghdad, Iraq.

⁴ Bilad Alrafidain University, College of Medical Technology, Diyala, Iraq.

10.31557/APJCP.2025.26.6.2117

Abstract

Objective: This study aimed to assess the combined impact of linagliptin and ciprofloxacin on inhibiting cervical cancer cell line proliferation and their ability to target heat shock protein 60. Methods: The anticancer properties of the linagliptin-ciprofloxacin combination were assessed employing the HeLa cervical cancer cell line, with incubation periods of 24 and 72 hours. The human fibroblast cell line (HFF) was utilized to evaluate the mixture’s safety. The concentrations of linagliptin, ciprofloxacin, and their combination varied between 0.1 and 1000 µg/ml. combination index value was estimated to assess the potential synergistic impact of linagliptin and ciprofloxacin. The study also employs computational molecular docking simulations to evaluate the affinity of linagliptin and ciprofloxacin for binding to heat shock protein 60. Results: The study’s findings demonstrated that the combination of linagliptin and ciprofloxacin markedly inhibited the proliferation of cervical cancer cells. The inhibitory effect depended on the concentration of the mixture and the incubation duration. It concurrently exhibits a diminished impact on the viability of the HFF cell line. The combination index study indicates that the interaction between linagliptin and ciprofloxacin shows a synergistic effect across all concentrations, particularly after 24 hours of incubation. The computational molecular docking simulation demonstrated that linagliptin and ciprofloxacin can bind with Hsp 60. The docking scores for linagliptin and ciprofloxacin were recorded at -7.6 kcal/mol and -8.1 kcal/mol, respectively. Conclusion: Our study findings from the MTT assay, combination index, and computational docking simulations indicate that the combination of linagliptin and ciprofloxacin presents a promising option for treating cervical cancer, considering their defined adverse effects and pharmacokinetic profiles.

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