Antiproliferative Impact of Linagliptin on the Cervical Cancer Cell Line

Muafaq Said, Ali; Abdulla, Kawakeb Najim; Ahmed, Nihad Hussein; Yasin, Youssef Shakuri

doi:10.31557/APJCP.2024.25.9.3293

Antiproliferative Impact of Linagliptin on the Cervical Cancer Cell Line

Document Type : Research Articles

Authors

¹ Al-Amarah University College, Iraq.

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

³ College of Pharmacy, Tikrit University, Tikrit, Iraq.

⁴ Bilad Alrafidain University College, Iraq.

10.31557/APJCP.2024.25.9.3293

Abstract

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

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