Indole-3-carbinol is produced from the cruciferous vegetables and broadly investigated for their various biological effects in in-vitro and in-vivo aspects. However, the anticancer activity of I3C and its molecular mechanisms have not been investigated in human adeno gastro carcinoma (AGS) cells. In our study of AGS cells, nuclear condensation was observed by 4',6-diamidino-2-phenylindole (DAPI) staining, cell death was confirmed by a cell viability assay, and fragmented DNA was observed at the IC50 dose by a DNA fragmentation assay. Apoptosis was evaluated by the qPCR technique. Treatment of the AGS cells with I3C at different concentrations has drastically decreased cell proliferation and differentiation. By releasing cytochrome-c from mitochondria in the intrinsic pathway, I3C prevents the multiplication of AGS cells and initiates apoptosis. The WST-1 assay result showed that I3C treatment against AGS cells had considerably reduced the viability of the cells. Furthermore, RT-qPCR showed the fold change among the expressed proteins compared with reference gene β-actin. Molecular docking revealed that I3C showed a strong binding affinity for the apoptotic protein 3DCY. The results show the caspase group of proteins contribute to the core of apoptotic machinery. I3C and its metabolites target a variety of components of cell-cycle control via distinct signaling pathways in light of the rapid development of tumors and oncogenesis. The translational significance of I3C and its metabolites in cancer is highlighted by their wide range of antitumor activity and low toxicity. Furthermore, the novel prodrug I3C, which has overlapping underlying mechanisms, could encourage new strategies to decrease oncogenesis.
Keywords: AGS cell; Indole-3-carbinol; apoptosis; gastric cancer; mitochondrial pathway.
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