Molla Mohammad Habibur Rahman, Aljahdali Mohammed Othman
Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21598, Saudi Arabia.
Saudi J Biol Sci. 2023 Sep;30(9):103748. doi: 10.1016/j.sjbs.2023.103748. Epub 2023 Jul 28.
Sea urchin-derived compounds are potential candidates for the development of effective drugs for the treatment of cancer diseases. In this study, 19 compounds derived from sea urchin () were used to treat colorectal cancer using the HCT116 cell line. However, molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamic (MD) simulation, and molecular mechanics generalized Born surface area (MM-GBSA) were used to confirm the ligand-protein interaction. Interactions of Importin-11 receptor with sea urchin compounds reveal that four compounds have higher binding affinities (ranging from -8.6 to -7.1 kcal/mol). In vitro testing revealed that the CID 6432458 compound was effective (docking score of -8.6 kcal/mol) against the HCT116 cell line. The cytotoxicity of HCT116 has been documented, with an IC50 value of 6.885 ± 4. MTT assay, apoptosis analysis, and cell cycle assay were utilized to examine cell death in colorectal cancer. In the MTT experiment, 15 µM and 20 µM dosages were associated with 77% cell death; however, flow cytometry analysis using the IC50 value revealed that the selected chemical induced greater apoptosis in the HCT116 cell line (58.5%). The gene expression data revealed that the apoptotic gene BAX is expressed at a higher level than the BCL-2 gene. The IPO11 gene was downregulated during treatment. In the experiment involving the cell cycle, the S phase for the 30 µM dose showed 75.1% apoptosis, which was greater than the other concentrations used alone. These in silico analysis will not only provide new information about Importin-11 receptor and insight into colorectal cancer but will also facilitate the development of natural compounds in a significant and worthwhile manner.
海胆衍生化合物是开发治疗癌症有效药物的潜在候选物。在本研究中，使用19种从海胆（）衍生的化合物，利用HCT116细胞系治疗结直肠癌。然而，通过分子对接、ADME（吸收、分布、代谢和排泄）、毒性、分子动力学（MD）模拟以及分子力学广义玻恩表面积（MM - GBSA）来确认配体 - 蛋白质相互作用。Importin - 11受体与海胆化合物的相互作用表明，四种化合物具有更高的结合亲和力（范围为 - 8.6至 - 7.1千卡/摩尔）。体外测试表明，CID 6432458化合物对HCT116细胞系有效（对接分数为 - 8.6千卡/摩尔）。已记录HCT116的细胞毒性，IC50值为6.885±4。利用MTT测定、凋亡分析和细胞周期测定来检查结直肠癌中的细胞死亡情况。在MTT实验中，15μM和20μM剂量导致77%的细胞死亡；然而，使用IC50值的流式细胞术分析表明，所选化学物质在HCT116细胞系中诱导了更高的凋亡率（58.5%）。基因表达数据显示，凋亡基因BAX的表达水平高于BCL - 2基因。在治疗过程中IPO11基因下调。在涉及细胞周期的实验中，30μM剂量的S期显示出75.1%的凋亡率，高于单独使用的其他浓度。这些计算机模拟分析不仅将提供有关Importin - 11受体的新信息以及对结直肠癌的深入了解，还将以重要且有价值的方式促进天然化合物的开发。
