Indole-3-carbinol induces apoptosis in AGS cancer cells via mitochondrial pathway
Alka Ashok Singh1, Sung-Han Jo2, Anley Teferra Kiddane1
1Laboratory of Cell Signaling, Department of Microbiology, College of Natural Science, Pukyong National University, Busan, Korea.
Abstract:
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.
Insights
Indole-3-carbinol (I3C) induces apoptosis in human gastric cancer cells by activating the intrinsic mitochondrial pathway. This cruciferous vegetable compound shows significant anticancer potential with low toxicity, offering new strategies against oncogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Indole-3-carbinol (I3C), derived from cruciferous vegetables, is known for various biological effects.
- The anticancer mechanisms of I3C in human gastric adenocarcinoma (AGS) cells remain largely unexplored.
Purpose of the Study:
- To investigate the anticancer activity and molecular mechanisms of I3C in human AGS cells.
- To evaluate I3C's effect on cell proliferation, apoptosis, and its binding affinity to apoptotic proteins.
Main Methods:
- Cell viability assays (WST-1) and DNA fragmentation assays were used to assess cell death.
- Quantitative PCR (qPCR) evaluated apoptosis markers and gene expression.
- Molecular docking identified I3C's binding affinity to apoptotic protein 3DCY.
Main Results:
- I3C significantly reduced AGS cell proliferation and viability.
- Nuclear condensation, DNA fragmentation, and cytochrome-c release indicated apoptosis induction via the intrinsic pathway.
- I3C demonstrated strong binding affinity for the apoptotic protein 3DCY, involving caspase activation.
Conclusions:
- I3C effectively induces apoptosis in human gastric cancer cells through intrinsic mitochondrial pathways.
- I3C and its metabolites exhibit broad-spectrum antitumor activity and low toxicity, suggesting potential for novel cancer therapeutic strategies.
- I3C's mechanisms offer promising avenues for developing new approaches to decrease oncogenesis.
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