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Diallyl trisulfide induces apoptosis of human basal cell carcinoma cells via endoplasmic reticulum stress and the mitochondrial pathway.
Nutr Cancer 2012; 64(5):770-80NC

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.

Authors+Show Affiliations

Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22519436

Citation

Wang, Hsiao-Chi, et al. "Diallyl Trisulfide Induces Apoptosis of Human Basal Cell Carcinoma Cells Via Endoplasmic Reticulum Stress and the Mitochondrial Pathway." Nutrition and Cancer, vol. 64, no. 5, 2012, pp. 770-80.
Wang HC, Hsieh SC, Yang JH, et al. Diallyl trisulfide induces apoptosis of human basal cell carcinoma cells via endoplasmic reticulum stress and the mitochondrial pathway. Nutr Cancer. 2012;64(5):770-80.
Wang, H. C., Hsieh, S. C., Yang, J. H., Lin, S. Y., & Sheen, L. Y. (2012). Diallyl trisulfide induces apoptosis of human basal cell carcinoma cells via endoplasmic reticulum stress and the mitochondrial pathway. Nutrition and Cancer, 64(5), pp. 770-80. doi:10.1080/01635581.2012.676142.
Wang HC, et al. Diallyl Trisulfide Induces Apoptosis of Human Basal Cell Carcinoma Cells Via Endoplasmic Reticulum Stress and the Mitochondrial Pathway. Nutr Cancer. 2012;64(5):770-80. PubMed PMID: 22519436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diallyl trisulfide induces apoptosis of human basal cell carcinoma cells via endoplasmic reticulum stress and the mitochondrial pathway. AU - Wang,Hsiao-Chi, AU - Hsieh,Shu-Chen, AU - Yang,Jen-Hung, AU - Lin,Shuw-Yuan, AU - Sheen,Lee-Yan, Y1 - 2012/04/20/ PY - 2012/4/24/entrez PY - 2012/4/24/pubmed PY - 2012/10/31/medline SP - 770 EP - 80 JF - Nutrition and cancer JO - Nutr Cancer VL - 64 IS - 5 N2 - 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. SN - 1532-7914 UR - https://www.unboundmedicine.com/medline/citation/22519436/Diallyl_trisulfide_induces_apoptosis_of_human_basal_cell_carcinoma_cells_via_endoplasmic_reticulum_stress_and_the_mitochondrial_pathway_ L2 - http://www.tandfonline.com/doi/full/10.1080/01635581.2012.676142 DB - PRIME DP - Unbound Medicine ER -