Breast Cancer Research and Treatment

, Volume 138, Issue 1, pp 69–79 | Cite as

Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic

  • Kumar Chandra-Kuntal
  • Joomin Lee
  • Shivendra V. SinghEmail author
Preclinical study


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.


Diallyl trisulfide Reactive oxygen species Apoptosis Chemoprevention 



Diallyl trisulfide




Reactive oxygen species




Dimethyl sulfoxide


Phosphate-buffered saline


Superoxide dismutase


Human epidermal growth factor receptor-2


Epithelial–mesenchymal transition


c-Jun NH2-terminal kinase


Heme oxygenase-1



Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number R01 CA113363-07 (to SVS). This research project used the Flow Cytometry Facility that was supported in part by a Grant from the National Cancer Institute at the National Institutes of Health under award number P30 CA047904.

Conflict of interest

KC-K, JL, and SVS declare no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kumar Chandra-Kuntal
    • 1
  • Joomin Lee
    • 1
  • Shivendra V. Singh
    • 1
    Email author
  1. 1.Department of Pharmacology & Chemical BiologyUniversity of Pittsburgh Cancer Institute, University of Pittsburgh School of MedicinePittsburghUSA

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