Diallyl trisulfide induces apoptosis in human breast cancer cells through ROS-mediated activation of JNK and AP-1

Forkhead Box Q1 Is a Novel Target of Breast Cancer Stem Cell Inhibition by Diallyl Trisulfide

“…Rare but serious and often life-threatening side effects are another limitation of the clinically used breast cancer preventive interventions such as tamoxifen (41,42). DATS appears promising for the prevention of breast cancer based on the following considerations: population-based studies suggest that garlic intake may lower breast cancer risk (8,9); dietary administration of garlic powder inhibits the incidence of chemically induced mammary cancer in rats (11, 12); DATS treatment inhibits the growth of cultured human breast cancer cells irrespective of the ER-␣ status (19); oral administration of DATS inhibits in vivo growth of MCF-7 xenografts in mice (18); a clinical intervention with 200 mg of synthetic DATS (Allitridum) every day plus 100 g of selenium every other day for 1 month showed acceptable tolerance (44); and bCSC fraction is decreased upon treatment with DATS in breast cancer cells representing luminal and basal subtypes, and DATS administration causes a decrease in ALDH1 activity in vivo in SUM159 xenografts (this study). Noticeably, bCSC inhibition by DATS is evident at a non-cytotoxic concentration.…”

“…For example, DATS treatment inhibited DNA strand breaks induced by an environmental carcinogen (benzo-[a]pyrene) in a non-tumorigenic normal human mammary epi-thelial cell line (MCF-10A) (16). Interestingly, DATS was found to be a much more potent inducer of apoptotic cell death in MCF-7 cells compared with its monosulfide (DAS) or disulfide (DADS) analogues (18). We have shown previously that breast cancer cells are much more sensitive to cell growth inhibition and apoptosis induction by DATS than normal human mammary epithelial cells (19).…”

“…Cellular models have been utilized to delineate the mechanisms by which garlic constituents may inhibit breast cancer growth (15)(16)(17)(18)(19)(20). For example, DATS treatment inhibited DNA strand breaks induced by an environmental carcinogen (benzo-[a]pyrene) in a non-tumorigenic normal human mammary epi-thelial cell line (MCF-10A) (16).…”

Halofuginone induces the apoptosis of breast cancer cells and inhibits migration via downregulation of matrix metalloproteinase-9

“…Therefore, various apoptotic pathways have been extensively investigated for many compounds to understand their cytotoxicity. A sensitive effector mechanism widely engaged in the control and modulation of apoptosis is cellular redox status, which is determined by the balance between the rates of generation and breakdown of reactive oxygen species (ROS) (8). ROS is a major regulator involved in apoptosis mediated through mitochondria.…”

Diallyl trisulfide induces apoptosis in Jurkat cells by the modification of cysteine residues in thioredoxin

“…[2][3][4] We also reported that DATS induces apoptosis in human colon cell lines by oxidative modification of cysteine residues in β-tubulin into S-allyl cysteine residues; this modification causes cell cycle arrest at M-phase followed by apoptosis. 5,6) On the other hand, we also found that DATS induces apoptosis in human leukemic cells in a cell cycle independent manner; however, the molecular target(s) of DATS remains to be clarified.…”