Diallyl trisulfide induces apoptosis of human basal cell carcinoma cells via endoplasmic reticulum stress and the mitochondrial pathwaya
Journal
Nutrition and Cancer
Journal Volume
64
Journal Issue
5
Pages
770-780
Date Issued
2012
Author(s)
Abstract
Diallyl trisulfide (DATS), an active component of garlic oil, has attracted much attention because of its anticancer effect on several types of cancers. However, the mechanism of DATS-induced apoptosis of basal cell carcinoma (BCC) is not fully understood. In the present study, we revealed that DATS-mediated dose-dependent induction of apoptosis in BCC cells was associated with intracellular reactive oxygen species accumulation and disrupted mitochondrial membrane potential. Western analysis demonstrated concordant expression of molecules involved in mitochondrial apoptosis, including DATS-associated increases in phospho-p53, proapoptotic Bax, and decreases in antiapoptotic Bcl-2 and Bcl-xl in BCC cells. Moreover, DATS induced the release of cytochrome c, apoptosis-inducing factor, and HtrA2/Omi into the cytoplasm, and activated factors downstream of caspase-dependent and caspase-independent apoptosis, including nuclear translocation of apoptotic-inducing factor and endonuclease G and the caspase cascade. These results were confirmed by pretreatment with the antioxidant N-acetyl-L-cysteine and the caspase inhibitor (z-VAD-fmk), the latter of which did not completely enhance the viability of DATS-treated BBC cells. Exposure to DATS additionally induced endogenous endoplasmic reticulum stress markers and intracellular Ca2+ mobilization, upregulation of Bip/GRP78 and CHOP/GADD153, and activation of caspase-4. Our findings suggest that DATS exerts chemopreventive potential via ER stress and the mitochondrial pathway in BCC cells. Copyright ? 2012, Taylor & Francis Group, LLC.
SDGs
Other Subjects
acetylcysteine; antineoplastic agent; apoptosis inducing factor; caspase 4; cytochrome c; diallyl trisulfide; endonuclease G; glucose regulated protein 78; growth arrest and DNA damage inducible protein 153; protein Bax; protein bcl 2; protein bcl x; protein p53; reactive oxygen metabolite; serine proteinase Omi; antineoplastic activity; apoptosis; article; basal cell carcinoma; calcium cell level; calcium mobilization; cell viability; controlled study; cytoplasm; endoplasmic reticulum stress; human; human cell; mitochondrial membrane potential; upregulation; Allyl Compounds; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Calcium Signaling; Carcinoma, Basal Cell; Cell Line, Tumor; Cell Nucleus; Cell Nucleus Shape; Cell Survival; Cysteine Proteinase Inhibitors; Endodeoxyribonucleases; Endoplasmic Reticulum Stress; Humans; Membrane Potential, Mitochondrial; Mitochondria; Protein Transport; Reactive Oxygen Species; Skin Neoplasms; Sulfides; Tumor Suppressor Protein p53; Allium sativum
Type
journal article