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Diallyl trisulfide induces apoptosis in human breast cancer cells through ROS-mediated activation of JNK and AP-1.
Biochem Pharmacol 2012; 84(10):1241-50BP

Abstract

Multiple lines of evidence support an inverse association between consumption of garlic and the risk of cancer. Chemopreventive effects of garlic have been attributed to its oil-soluble sulfur ingredients, such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), but their underlying molecular mechanisms remain largely unresolved. In the present study, we found that DATS showed the most potent anti-proliferative effects in human breast cancer MCF-7 cells. MCF-7 cells treated with DATS underwent apoptotic death as revealed by a progressive increase in the proportion of the sub-G0/G1 cell population and a typical pattern of annexin V/propidium iodide staining. DATS induced phosphorylation of the antiapoptotic Bcl-2 and proteolytic cleavage of poly(ADP-ribose)polymerase (PARP) in MCF-7 cells. DATS treatment activated c-Jun N-terminal kinase (JNK). DATS-induced apoptosis was blunted in MCF-7 cells treated with a specific JNK inhibitor SP600125 or transiently transfected with dominant negative JNK. DATS treatment resulted in accumulation of reactive oxygen species (ROS). DATS-induced apoptosis as well as activation of JNK was abrogated by N-acetyl-l-cysteine (NAC). Furthermore, DATS induced phosphorylation and expression of c-Jun, which were attenuated by NAC. MCF-7 cells treated with DATS also exhibited increased DNA binding activity of AP-1, which was blocked by NAC and the JNK inhibitor. Proteolytic cleavage of PARP induced by DATS was abrogated in the cells transfected with c-jun siRNA. Oral administration of 5μmol/kg DATS to female Balb/c mice inhibited the growth of human MCF-7 cell tumor xenografts. These results suggest that DATS-induced apoptosis is mediated through ROS generation and subsequent activation of JNK and AP-1.

Authors+Show Affiliations

Department of Food & Nutrition, College of Human Ecology, Sungshin Women's University, Seoul, South Korea. nhkdec28@gmail.comNo affiliation info availableNo 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

22981381

Citation

Na, Hye-Kyung, et al. "Diallyl Trisulfide Induces Apoptosis in Human Breast Cancer Cells Through ROS-mediated Activation of JNK and AP-1." Biochemical Pharmacology, vol. 84, no. 10, 2012, pp. 1241-50.
Na HK, Kim EH, Choi MA, et al. Diallyl trisulfide induces apoptosis in human breast cancer cells through ROS-mediated activation of JNK and AP-1. Biochem Pharmacol. 2012;84(10):1241-50.
Na, H. K., Kim, E. H., Choi, M. A., Park, J. M., Kim, D. H., & Surh, Y. J. (2012). Diallyl trisulfide induces apoptosis in human breast cancer cells through ROS-mediated activation of JNK and AP-1. Biochemical Pharmacology, 84(10), pp. 1241-50. doi:10.1016/j.bcp.2012.08.024.
Na HK, et al. Diallyl Trisulfide Induces Apoptosis in Human Breast Cancer Cells Through ROS-mediated Activation of JNK and AP-1. Biochem Pharmacol. 2012 Nov 15;84(10):1241-50. PubMed PMID: 22981381.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diallyl trisulfide induces apoptosis in human breast cancer cells through ROS-mediated activation of JNK and AP-1. AU - Na,Hye-Kyung, AU - Kim,Eun-Hee, AU - Choi,Min-Ah, AU - Park,Jong-Min, AU - Kim,Do-Hee, AU - Surh,Young-Joon, Y1 - 2012/09/06/ PY - 2012/06/12/received PY - 2012/08/27/revised PY - 2012/08/29/accepted PY - 2012/9/18/entrez PY - 2012/9/18/pubmed PY - 2013/1/19/medline SP - 1241 EP - 50 JF - Biochemical pharmacology JO - Biochem. Pharmacol. VL - 84 IS - 10 N2 - Multiple lines of evidence support an inverse association between consumption of garlic and the risk of cancer. Chemopreventive effects of garlic have been attributed to its oil-soluble sulfur ingredients, such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), but their underlying molecular mechanisms remain largely unresolved. In the present study, we found that DATS showed the most potent anti-proliferative effects in human breast cancer MCF-7 cells. MCF-7 cells treated with DATS underwent apoptotic death as revealed by a progressive increase in the proportion of the sub-G0/G1 cell population and a typical pattern of annexin V/propidium iodide staining. DATS induced phosphorylation of the antiapoptotic Bcl-2 and proteolytic cleavage of poly(ADP-ribose)polymerase (PARP) in MCF-7 cells. DATS treatment activated c-Jun N-terminal kinase (JNK). DATS-induced apoptosis was blunted in MCF-7 cells treated with a specific JNK inhibitor SP600125 or transiently transfected with dominant negative JNK. DATS treatment resulted in accumulation of reactive oxygen species (ROS). DATS-induced apoptosis as well as activation of JNK was abrogated by N-acetyl-l-cysteine (NAC). Furthermore, DATS induced phosphorylation and expression of c-Jun, which were attenuated by NAC. MCF-7 cells treated with DATS also exhibited increased DNA binding activity of AP-1, which was blocked by NAC and the JNK inhibitor. Proteolytic cleavage of PARP induced by DATS was abrogated in the cells transfected with c-jun siRNA. Oral administration of 5μmol/kg DATS to female Balb/c mice inhibited the growth of human MCF-7 cell tumor xenografts. These results suggest that DATS-induced apoptosis is mediated through ROS generation and subsequent activation of JNK and AP-1. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/22981381/Diallyl_trisulfide_induces_apoptosis_in_human_breast_cancer_cells_through_ROS_mediated_activation_of_JNK_and_AP_1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(12)00580-1 DB - PRIME DP - Unbound Medicine ER -