Benzyl Isothiocyanate Induces Apoptosis via Reactive Oxygen Species-Initiated Mitochondrial Dysfunction and DR4 and DR5 Death Receptor Activation in Gastric Adenocarcinoma Cells.

Abstract

Benzyl isothiocyanate (BITC) is known to inhibit the metastasis of gastric cancer cells but further studies are needed to confirm its chemotherapeutic potential against gastric cancer. In this study, we observed cell shrinkage and morphological changes in one of the gastric adenocarcinoma cell lines, the AGS cells, after BITC treatment. We performed 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2H-tetrazolium bromide (MTT) assay, a cell viability assay, and found that BITC decreased AGS cell viability. Reactive oxygen species (ROS) analyses using 2',7'-dichlorofluorescin diacetate (DCFDA) revealed that BITC-induced cell death involved intracellular ROS production, which resulted in mitochondrial dysfunction. Additionally, cell viability was partially restored when BITC-treated AGS cells were preincubated with glutathione (GSH). Western blotting indicated that BITC regulated the expressions of the mitochondria-mediated apoptosis signaling molecules, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cytochrome c (Cyt c). In addition, BITC increased death receptor DR5 expression, and activated the cysteine-aspartic proteases (caspases) cascade. Overall, our results showed that BITC triggers apoptosis in AGS cells via the apoptotic pathways involved in ROS-promoted mitochondrial dysfunction and death receptor activation.

• Authors: Khin Wah Wah Han, Wah Wah Po, Uy Dong Sohn, Hyun-Jung Kim
• Journal: Biomolecules (Biomolecules) Vol. 9 Issue 12 (12 06 2019) ISSN: 2218-273X [Electronic] Switzerland
• PMID: 31817791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biological Products
• Isothiocyanates
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNFRSF10A protein, human
• TNFRSF10B protein, human
• bcl-2-Associated X Protein
• benzyl isothiocyanate
• Cytochromes c

Topics

• Adenocarcinoma (drug therapy, metabolism, secondary)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Biological Products (pharmacology)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cytochromes c (drug effects, metabolism)
• Humans
• Isothiocyanates (pharmacology)
• Mitochondria (metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (drug effects, metabolism)
• Reactive Oxygen Species (metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (drug effects, metabolism)
• Signal Transduction (drug effects)
• Stomach Neoplasms (drug therapy, metabolism, secondary)
• bcl-2-Associated X Protein (drug effects, metabolism)