Al-Amarah University College, Iraq.
Iraqi National Cancer Research Center, University of Baghdad, Baghdad, Iraq.
Asian Pac J Cancer Prev. 2024 Sep 1;25(9):3293-3300. doi: 10.31557/APJCP.2024.25.9.3293.
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.
本研究旨在评估利拉利汀对宫颈癌细胞系增殖的抑制作用，并研究其靶向人热休克蛋白 90 的潜力。
在两个不同的孵育期（24 小时和 72 小时），使用利拉利汀评估宫颈癌细胞系（Hela 癌细胞系）的细胞毒性。使用 Biovia Discovery Studio 和 AutoDock 工具软件对利拉利汀和受体蛋白人 Hsp 90（PDB 代码：5XRE）之间的分子对接进行了研究。Discovery Studio 可视化器生成了三维（3D）和二维（2D）交互式图像。
该研究的细胞毒性结果表明，利拉利汀可以抑制宫颈癌细胞的增殖。细胞毒性表现出时间依赖性模式（细胞周期特异性）。进行分子对接研究以研究利拉利汀与人 Hsp90 之间的相互作用。研究确定了利拉利汀可以与 Hsp90 氨基酸残基结合的 11 个位点。这种相互作用的总对接得分为-10.3 kcal/mol。最有效的结合是通过与 ASP：54 氨基酸残基的常规氢键发生的，距离为 2.93 Å。利拉利汀的对接得分与参考药物格尔德霉素相当，表明利拉利汀与 Hsp90 之间存在强烈的相互作用。
该研究发现，利拉利汀成功地降低了宫颈癌细胞的生长速度，具有时间依赖性的细胞毒性模式。通过分析利拉利汀与 Hsp90 之间的对接得分和对接模式，可以推断出利拉利汀的潜在抗癌机制，表明利拉利汀靶向人 Hsp 90。
