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Diallyl trisulfide selectively causes Bax- and Bak-mediated apoptosis in human lung cancer cells.
Environ Mol Mutagen. 2009 Apr; 50(3):201-12.EM

Abstract

Garlic-derived organosulfur compounds (OSCs) are highly effective in affording protection against chemically induced pulmonary carcinogenesis in animal models. We now demonstrate that garlic constituent diallyl trisulfide (DATS) suppresses viability of cultured human lung cancer cell lines H358 (anon-small cell lung cancer cell line) and H460 (a large cell lung cancer cell line) by causing G2-M phase cell cycle arrest and apoptotic cell death. On the other hand, a normal human bronchial epithelial cell line BEAS-2B was significantly more resistant to growth inhibition and apoptosis induction by DATS compared with lung cancer cells. We also found that even a subtle change in the OSC structure could have a significant impact on its biological activity. For example, DATS was significantly more effective than either diallyl sulfide or diallyl disulfide against proliferation of lung cancer cells. The DATS-mediated G2-M phase cell cycle arrest was explained by down-regulation of cyclin-dependent kinase 1 (Cdk1) and cell division cycle 25C protein expression leading to accumulation of Tyr15 phosphorylated (inactive) Cdk1. The DATS-induced apoptosis correlated with induction of pro-apoptotic proteins Bax, Bak and BID, and a decrease in the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL in lung cancer cells but not in BEAS-2B. Knockdown of Bax and Bak proteins conferred significant protection against DATS-induced apoptotic cytoplasmic histone-associated DNA fragmentation. On the other hand, BID protein was dispensable for DATS-induced apoptosis. In conclusion, the present study indicates that Bax and Bak proteins are critical targets of DATS-induced apoptosis in human lung cancer cells.

Authors+Show Affiliations

Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18800351

Citation

Xiao, Dong, et al. "Diallyl Trisulfide Selectively Causes Bax- and Bak-mediated Apoptosis in Human Lung Cancer Cells." Environmental and Molecular Mutagenesis, vol. 50, no. 3, 2009, pp. 201-12.
Xiao D, Zeng Y, Hahm ER, et al. Diallyl trisulfide selectively causes Bax- and Bak-mediated apoptosis in human lung cancer cells. Environ Mol Mutagen. 2009;50(3):201-12.
Xiao, D., Zeng, Y., Hahm, E. R., Kim, Y. A., Ramalingam, S., & Singh, S. V. (2009). Diallyl trisulfide selectively causes Bax- and Bak-mediated apoptosis in human lung cancer cells. Environmental and Molecular Mutagenesis, 50(3), 201-12. https://doi.org/10.1002/em.20431
Xiao D, et al. Diallyl Trisulfide Selectively Causes Bax- and Bak-mediated Apoptosis in Human Lung Cancer Cells. Environ Mol Mutagen. 2009;50(3):201-12. PubMed PMID: 18800351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diallyl trisulfide selectively causes Bax- and Bak-mediated apoptosis in human lung cancer cells. AU - Xiao,Dong, AU - Zeng,Yan, AU - Hahm,Eun-Ryeong, AU - Kim,Young-Ae, AU - Ramalingam,Suresh, AU - Singh,Shivendra V, PY - 2008/9/19/pubmed PY - 2009/3/28/medline PY - 2008/9/19/entrez SP - 201 EP - 12 JF - Environmental and molecular mutagenesis JO - Environ Mol Mutagen VL - 50 IS - 3 N2 - Garlic-derived organosulfur compounds (OSCs) are highly effective in affording protection against chemically induced pulmonary carcinogenesis in animal models. We now demonstrate that garlic constituent diallyl trisulfide (DATS) suppresses viability of cultured human lung cancer cell lines H358 (anon-small cell lung cancer cell line) and H460 (a large cell lung cancer cell line) by causing G2-M phase cell cycle arrest and apoptotic cell death. On the other hand, a normal human bronchial epithelial cell line BEAS-2B was significantly more resistant to growth inhibition and apoptosis induction by DATS compared with lung cancer cells. We also found that even a subtle change in the OSC structure could have a significant impact on its biological activity. For example, DATS was significantly more effective than either diallyl sulfide or diallyl disulfide against proliferation of lung cancer cells. The DATS-mediated G2-M phase cell cycle arrest was explained by down-regulation of cyclin-dependent kinase 1 (Cdk1) and cell division cycle 25C protein expression leading to accumulation of Tyr15 phosphorylated (inactive) Cdk1. The DATS-induced apoptosis correlated with induction of pro-apoptotic proteins Bax, Bak and BID, and a decrease in the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL in lung cancer cells but not in BEAS-2B. Knockdown of Bax and Bak proteins conferred significant protection against DATS-induced apoptotic cytoplasmic histone-associated DNA fragmentation. On the other hand, BID protein was dispensable for DATS-induced apoptosis. In conclusion, the present study indicates that Bax and Bak proteins are critical targets of DATS-induced apoptosis in human lung cancer cells. SN - 1098-2280 UR - https://www.unboundmedicine.com/medline/citation/18800351/Diallyl_trisulfide_selectively_causes_Bax__and_Bak_mediated_apoptosis_in_human_lung_cancer_cells_ L2 - https://doi.org/10.1002/em.20431 DB - PRIME DP - Unbound Medicine ER -