Diallyl trisulfide (DATS) is a bioactive component of processed garlic with in vivo activity against chemically-induced as well as oncogene-driven cancer in rodent models. However, the mechanisms underlying anticancer effects of DATS (eg, growth inhibition, apoptosis induction, and suppression of migration in cancer cells) are not fully understood. The present study reveals a critical role for reactive oxygen species (ROS) in cellular anticancer responses to DATS. Exposure of human breast cancer cells (MDA-MB-231 and MCF-7) as well as a cell line derived from spontaneously developing mammary tumor of a MMTV-neu transgenic mouse (BRI-JM04) to DATS resulted in dose-dependent inhibition of cell viability and apoptosis induction. Interestingly, 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 ROS production as evidenced by fluorescence microscopy and flow cytometry using a chemical probe (MitoSOX Red). Ectopic expression 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. The DATS treatment caused activation of Bax and Bak, and activation of Bak was nearly fully abolished by overexpression of Mn-SOD. Likewise, inhibition of MDA-MB-231 and MCF-7 cell migration resulting from DATS treatment was partially but statistically significantly attenuated by stable overexpression of Cu,Zn-SOD and Mn-SOD. This protection against inhibition of cell migration was attributable to abrogation of DATS-mediated induction of E-cadherin and suppression of vimentin. These results indicate that ROS play an important role in anticancer effects of DATS at least in human breast cancer cells. This study was supported by grant CA113363-07 awarded by the National Cancer Institute.
Citation Format: Julie A. Arlotti, Kumar Chandra-Kuntal, Shivendra V. Singh. The role of reactive oxygen species in anticancer effects of diallyl trisulfide, a bioactive component of garlic. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3670. doi:10.1158/1538-7445.AM2013-3670