Diallyltrisulfide induced oral cancer cells apoptosis through ROS generation
Date Issued
2008
Date
2008
Author(s)
Chuang, Yuan-Ting
Abstract
Epidemiological studies support the premise that dietary intake of Allium vegetables (e.g., garlic, onions and so forth) may lower the risk of varies types of cancer. Garlic-derived compounds have been shown to offer protection against oral tumor in animal models induced by carcinogens. Garlic-derived organosulfur compounds (OSCs) including diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) have been shown to suppress proliferation and induce apoptosis in various cancer cell lines including skin, intestinal, breast and colon cancer cells. Previously, we have shown that DATS can induce apoptosis in oral cancer SAS and Ca9-22 cell lines. DATS was more effective than DAS and DADS for induction of apoptosis. However, the effects of DATS on oral cancer cells are not fully understood.n this study, we found treatment of SAS and Ca9-22 cells with DATS induced reactive oxygen species (ROS) production as detected by DCF fluorescence. Pretreatment of cells with NAC reduced the DATS-induced apoptosis. We also found that DATS-PDT was able to induced JNK activation and pretreatment of cells with SP600125 (JNK inhibitor) inhibited DATS -induced PARP cleavage. Western blot analysis showed DATS treatment induced FADD overexpression, Bcl-2 down-regulation, caspase-8, caspase-9 activation and PARP cleavage. We also observed that treatment of Ca9-22 cells with DATS activated of caspase-4, which indicated involvement of endoplasmic reticulum (ER) stress in apoptosis.aken together, our study showed that DATS can induce apoptosis in oral cancer cells via ROS production, JNK phosphorylation, activating intrinsic- and extrinsic-apoptosis pathway, and caspase-4 activation.
Subjects
oral cancer
apoptosis
ROS
SDGs
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