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.

A Combined Phytochemistry and Network Pharmacology Approach to Reveal Potential Anti-NSCLC Effective Substances and Mechanisms in Marsdenia tenacissima (Roxb.) Moon (Stem)

“…Apoptosis induction is considered an essential mechanism of antitumor therapeutics ( Stepczynska et al, 2001 ). Previous studies have revealed that anticancer agents impart anti-proliferative effects using two distinct apoptosis pathways that involve mitochondria or death receptors ( Kuo et al, 2018 ; Han et al, 2019 ). Specifically, the mitochondria-associated pathway is a classic intrinsic pathway that is caused by ROS overproduction, which in turn results in the depletion of △φin ( Shi et al, 2014 ; Wang et al, 2019 ).…”

2,3,4′,5-Tetrahydroxystilbene-2-O-β-D-Glucoside (THSG) Activates the Nrf2 Antioxidant Pathway and Attenuates Oxidative Stress-Induced Cell Death in Mouse Cochlear UB/OC-2 Cells

“…Caspase 9, the initiator caspase in the mitochondria-dependent apoptosis pathway, activates the downstream effector Caspase 3, and active Caspase 3 impairs DNA repair through the cleavage of poly ADP-ribose polymerase (PARP). Excess ROS upregulate autophagy to remove proteins and organelles with oxidative damage in the cytoplasm [18][19][20][21]. LC3-phosphatidylethanolamine conjugate (LC3-II), a marker for autophagy, is involved in the formation of autophagosome membranes, and autophagosomes might fuse with lysosomes to degrade damaged cytosolic components [22][23][24][25].…”

Transcriptomic Analysis, Motility and Biofilm Formation Characteristics of Salmonella typhimurium Exposed to Benzyl Isothiocyanate Treatment

“…This highlights that BITC is a good natural product for inhibiting S. typhimurium. Moreover, it has been proven by a large number of experimental studies that the antibacterial effect of BITC against foodborne pathogens is of great significance for food safety and clinical research [12,[28][29][30].…”

“…Benzyl isothiocyanate (BITC) which is extensively found in senvy, pilu oil, cruciferous plants and papaya seeds [11], has been shown to exert potential health benefits to humans. According to the recent studies, BITC shows excellent therapeutic effects on cancer by reversing or blocking the proliferation of DNA-damaged precancerous cells [12][13][14]. In addition, BITC antibacterial mechanisms in foodborne bacteria have been widely studied.…”