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 (Diadema savignyi) 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 and in vitro 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.
Keywords: Colorectal cancer; GC–MS; IPO11; MD simulation; MM/GBSA; Molecular docking; Sea urchin.
© 2023 The Author(s).