Molla MHR and Aljahdali MO (2023), Marine-derived sea urchin compounds as potentia...

ECB-ART-51717

Saudi J Biol Sci 2023 Sep 01;309:103748. doi: 10.1016/j.sjbs.2023.103748.

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Marine-derived sea urchin compounds as potential anti-cancer drug candidate against colorectal cancer: In silico and in vitro studies.

Molla MHR , Aljahdali MO .

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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.

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	Fig. 1. Active pocket showing the amino acid residue, volume and area. The first active pocket are marked in A1 with purple, A2 with yellow, A3 with blue, and A4 with red colour, respectively.
	Fig. 2. RMSD values calculated from four selected compounds with Apoprotein.
	Fig. 3. RMSF values calculated from the four selected compounds with Apoprotein.
	Fig. 4. The figure show the contact ratio of various ligands from the sea urchin with receptor.
	Fig. 5. MM/GBSA calculation from the selected four compounds.
	Fig. 6. The cell viability of the HCT116 cell line and cell death at various concentrations.
	Fig. 7. Quantification of apoptosis-induced cell death by Flow Cytometry.
	Fig. 8. CID 6432458 inhibited progression of the HCT116 cell line through the S and G0/G1 phases of the cell cycle.
	Fig. 9. The qPCR analysis of apoptotic genes (Bcl-2, Bax, and IPO11) in HCT116 cells. The HCT116 cells were treated with a sea urchin compound for 48, 72, and 96 h and identified the expression of Bcl-2, Bax, and IPO11 (A). GAPDH was used as a control for the relative expression of other genes (B).