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Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic.
Breast Cancer Res Treat 2013; 138(1):69-79BC

Abstract

Diallyl trisulfide (DATS) is a structurally simple but biologically active constituent of processed garlic with in vivo activity against chemically induced as well as oncogene-driven cancer in experimental rodents. This study offers novel insights into the mechanisms underlying anticancer effects of DATS using human breast cancer cells as a model. Exposure of human breast cancer cells (MCF-7 and MDA-MB-231) and a cell line derived from spontaneously developing mammary tumor of a transgenic mouse (BRI-JM04) to DATS resulted in a dose-dependent inhibition of cell viability that was accompanied by apoptosis induction. A non-tumorigenic normal human mammary cell line (MCF-10A) was resistant to growth inhibition and apoptosis induction by DATS. The DATS-induced apoptosis in MDA-MB-231, MCF-7, and BRI-JM04 cells was associated with reactive oxygen species (ROS) production as evidenced by fluorescence microscopy and flow cytometry using a chemical probe (MitoSOX Red). Overexpression of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) as well as Mn-SOD conferred significant protection against DATS-induced ROS production and apoptotic cell death in MDA-MB-231 and MCF-7 cells. Activation of Bak, but not Bax, resulting from DATS treatment was markedly suppressed by overexpression of Mn-SOD. The DATS treatment caused ROS generation, but not activation of Bax or Bak, in MCF-10A cells. Furthermore, the DATS-mediated inhibition of cell migration was partially but significantly attenuated by Cu,Zn-SOD and Mn-SOD overexpression in association with changes in levels of proteins involved in epithelial-mesenchymal transition. The DATS-mediated induction of heme oxygenase-1 was partially attenuated by overexpression of Mn-SOD. These results provide novel mechanistic insights indicating a critical role for ROS in anticancer effects of DATS.

Authors+Show Affiliations

Department of Pharmacology & Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 2.32A Hillman Cancer Center Research Pavilion, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23412769

Citation

Chandra-Kuntal, Kumar, et al. "Critical Role for Reactive Oxygen Species in Apoptosis Induction and Cell Migration Inhibition By Diallyl Trisulfide, a Cancer Chemopreventive Component of Garlic." Breast Cancer Research and Treatment, vol. 138, no. 1, 2013, pp. 69-79.
Chandra-Kuntal K, Lee J, Singh SV. Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic. Breast Cancer Res Treat. 2013;138(1):69-79.
Chandra-Kuntal, K., Lee, J., & Singh, S. V. (2013). Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic. Breast Cancer Research and Treatment, 138(1), pp. 69-79. doi:10.1007/s10549-013-2440-2.
Chandra-Kuntal K, Lee J, Singh SV. Critical Role for Reactive Oxygen Species in Apoptosis Induction and Cell Migration Inhibition By Diallyl Trisulfide, a Cancer Chemopreventive Component of Garlic. Breast Cancer Res Treat. 2013;138(1):69-79. PubMed PMID: 23412769.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic. AU - Chandra-Kuntal,Kumar, AU - Lee,Joomin, AU - Singh,Shivendra V, Y1 - 2013/02/15/ PY - 2012/10/21/received PY - 2013/01/31/accepted PY - 2013/2/16/entrez PY - 2013/2/16/pubmed PY - 2013/8/21/medline SP - 69 EP - 79 JF - Breast cancer research and treatment JO - Breast Cancer Res. Treat. VL - 138 IS - 1 N2 - Diallyl trisulfide (DATS) is a structurally simple but biologically active constituent of processed garlic with in vivo activity against chemically induced as well as oncogene-driven cancer in experimental rodents. This study offers novel insights into the mechanisms underlying anticancer effects of DATS using human breast cancer cells as a model. Exposure of human breast cancer cells (MCF-7 and MDA-MB-231) and a cell line derived from spontaneously developing mammary tumor of a transgenic mouse (BRI-JM04) to DATS resulted in a dose-dependent inhibition of cell viability that was accompanied by apoptosis induction. A non-tumorigenic normal human mammary cell line (MCF-10A) was resistant to growth inhibition and apoptosis induction by DATS. The DATS-induced apoptosis in MDA-MB-231, MCF-7, and BRI-JM04 cells was associated with reactive oxygen species (ROS) production as evidenced by fluorescence microscopy and flow cytometry using a chemical probe (MitoSOX Red). Overexpression of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) as well as Mn-SOD conferred significant protection against DATS-induced ROS production and apoptotic cell death in MDA-MB-231 and MCF-7 cells. Activation of Bak, but not Bax, resulting from DATS treatment was markedly suppressed by overexpression of Mn-SOD. The DATS treatment caused ROS generation, but not activation of Bax or Bak, in MCF-10A cells. Furthermore, the DATS-mediated inhibition of cell migration was partially but significantly attenuated by Cu,Zn-SOD and Mn-SOD overexpression in association with changes in levels of proteins involved in epithelial-mesenchymal transition. The DATS-mediated induction of heme oxygenase-1 was partially attenuated by overexpression of Mn-SOD. These results provide novel mechanistic insights indicating a critical role for ROS in anticancer effects of DATS. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/23412769/Critical_role_for_reactive_oxygen_species_in_apoptosis_induction_and_cell_migration_inhibition_by_diallyl_trisulfide_a_cancer_chemopreventive_component_of_garlic_ L2 - https://doi.org/10.1007/s10549-013-2440-2 DB - PRIME DP - Unbound Medicine ER -