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Apoptosis induction in human lung adenocarcinoma cells by oil-soluble allyl sulfides: triggers, pathways, and modulators.
Environ Mol Mutagen 2009; 50(3):266-75EM

Abstract

DAS (diallyl sulfide), DADS (diallyl disulfide), and DATS (diallyl trisulfide) are major oil-soluble allyl sulfides (OAS) that represent major garlic constituents. The anticarcinogenic and antimutagenic effects of these substances have been extensively studied during the last decades. Previous reports suggest that induction of apoptosis by OASs might contribute to their chemopreventive effects. In this study, we report that OASs DADS and DATS induce significant apoptosis in human lung adenocarcinoma A549 cells, whereas DAS does not. Differential modulation of reactive oxygen intermediates (ROI) and mitochondria membrane potential (MMP) may account for the apoptotic effects of DADS and DATS. The underlying molecular mechanisms of apoptosis induction by both compounds include activation of C-Jun N-terminal kinase (JNK), up-regulation of p53, and down-regulation of bcl-2 expression. In our test series, up-regulation of extracellular signal-regulated protein kinase (ERK) was dispensable for apoptosis induction; DAS, DADS, or DATS did not modify expression of MAPK p38, bax, and bcl-xL. Further investigation revealed that the specific JNK inhibitor SP600125 and the antioxidant NAC blocked DADS and DATS-induced apoptosis, whereas ERK inhibitors did not. Additionally, our data provide the first evidence that Fas-mediated cell death pathway is partly involved in DADS but not DATS-mediated cell death. Taken together, our work has elucidated the triggers, important modulators, and signal transduction pathways in DADS and DATS-mediated apoptosis.

Authors+Show Affiliations

University Medical Center Freiburg, Institute of Environmental Medicine and Hospital Hygiene, Freiburg, Germany. toxwu@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19197990

Citation

Wu, Xin-Jiang, et al. "Apoptosis Induction in Human Lung Adenocarcinoma Cells By Oil-soluble Allyl Sulfides: Triggers, Pathways, and Modulators." Environmental and Molecular Mutagenesis, vol. 50, no. 3, 2009, pp. 266-75.
Wu XJ, Hu Y, Lamy E, et al. Apoptosis induction in human lung adenocarcinoma cells by oil-soluble allyl sulfides: triggers, pathways, and modulators. Environ Mol Mutagen. 2009;50(3):266-75.
Wu, X. J., Hu, Y., Lamy, E., & Mersch-Sundermann, V. (2009). Apoptosis induction in human lung adenocarcinoma cells by oil-soluble allyl sulfides: triggers, pathways, and modulators. Environmental and Molecular Mutagenesis, 50(3), pp. 266-75. doi:10.1002/em.20467.
Wu XJ, et al. Apoptosis Induction in Human Lung Adenocarcinoma Cells By Oil-soluble Allyl Sulfides: Triggers, Pathways, and Modulators. Environ Mol Mutagen. 2009;50(3):266-75. PubMed PMID: 19197990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apoptosis induction in human lung adenocarcinoma cells by oil-soluble allyl sulfides: triggers, pathways, and modulators. AU - Wu,Xin-Jiang, AU - Hu,Ying, AU - Lamy,Evelyn, AU - Mersch-Sundermann,Volker, PY - 2009/2/7/entrez PY - 2009/2/7/pubmed PY - 2009/3/28/medline SP - 266 EP - 75 JF - Environmental and molecular mutagenesis JO - Environ. Mol. Mutagen. VL - 50 IS - 3 N2 - DAS (diallyl sulfide), DADS (diallyl disulfide), and DATS (diallyl trisulfide) are major oil-soluble allyl sulfides (OAS) that represent major garlic constituents. The anticarcinogenic and antimutagenic effects of these substances have been extensively studied during the last decades. Previous reports suggest that induction of apoptosis by OASs might contribute to their chemopreventive effects. In this study, we report that OASs DADS and DATS induce significant apoptosis in human lung adenocarcinoma A549 cells, whereas DAS does not. Differential modulation of reactive oxygen intermediates (ROI) and mitochondria membrane potential (MMP) may account for the apoptotic effects of DADS and DATS. The underlying molecular mechanisms of apoptosis induction by both compounds include activation of C-Jun N-terminal kinase (JNK), up-regulation of p53, and down-regulation of bcl-2 expression. In our test series, up-regulation of extracellular signal-regulated protein kinase (ERK) was dispensable for apoptosis induction; DAS, DADS, or DATS did not modify expression of MAPK p38, bax, and bcl-xL. Further investigation revealed that the specific JNK inhibitor SP600125 and the antioxidant NAC blocked DADS and DATS-induced apoptosis, whereas ERK inhibitors did not. Additionally, our data provide the first evidence that Fas-mediated cell death pathway is partly involved in DADS but not DATS-mediated cell death. Taken together, our work has elucidated the triggers, important modulators, and signal transduction pathways in DADS and DATS-mediated apoptosis. SN - 1098-2280 UR - https://www.unboundmedicine.com/medline/citation/19197990/Apoptosis_induction_in_human_lung_adenocarcinoma_cells_by_oil_soluble_allyl_sulfides:_triggers_pathways_and_modulators_ L2 - https://doi.org/10.1002/em.20467 DB - PRIME DP - Unbound Medicine ER -