Garlic-derived organosulfides induce cytotoxicity, apoptosis, cell cycle arrest and oxidative stress in human colon carcinoma cell lines.

Organosulfur compounds (OSC) from garlic, especially allicin (ALI), diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS) are recognized as a group of potential chemopreventive agents. In this study, we examined the effects of OSC on human Caco-2 and HT-29 colon carcinoma cell lines. Apoptosis induction (Annexin-V-FITC/PI, fluorescein diacetate/PI, sub-G1 fraction), modulation of DNA cell cycle (G2/M arrest, phospho-H3 mitotic marker), transmembrane mitochondrial potential (JC-1) and intracellular GSH amount (monochlorobimane assay) were measured by flow cytometry and fluorimetry. Our results showed that order of OSC-induced cell death in Caco-2 and HT-29 cells increased in the range as follows: ALI < DAS = DADS < DATS and ALI = DAS < DADS < DATS, respectively. Both cell lines used are relatively resistant to OSC induced cytotoxicity, because compound concentrations required to obtain significant effect are in high micromolar range. ALI was less toxic than equimolar doses of other OSC tested with the exception of GSH modulation and G2/M arrest in Caco-2 cells. DADS-treated HT-29 cells and both DATS-treated cell lines exhibit inverse correlation between p-H3 positivity and compound concentration due to higher apoptotic rate. These results show the correlation of sulfur atoms number in OSC with their capacity in apoptosis induction and support the role of redox-sensitive "sulfhydryl switches" in maintaining intracellular redox milieu.