Diallyl Disulfide Enhances Daunorubicin-Induced Apoptosis of HL-60 Cells

Dially disulfide (DADS), a component of garlic (Allium sativum), has been known to exert potent chemopreventive activity against various cancers. In this study, the synergistic effect of DADS and daunorubicin on the cytotoxicity of HL-60 cells, a human leukemia cell line, was investigated. DADS at 25 M greatly potentiated daunorubicin-induced cell death, decreasing cell viabilityto50%ofthe control. Daunorubicin-induced apoptosis was accompanied by the activation of caspase-3, the degradation of poly-(ADP-ribose) polymerase (PARP) and D4-GDI, and DNA fragmentation, which were blocked by pre-treatment with acetyl-Asp-Glu-Val-Asp- dialdehyde (Ac-DEVD-CHO). Treatment that combined 25 M DADS and 100 nM daunorubicin caused a similar degree of caspase-3 activation, PARP and D4-GDI degradation, and DNA fragmentation to that caused by treatment with 250 nM daunorubicin alone. These results indicate that combined therapy using daunorubicin with DADS, a component of food, and garlic can effectively decrease the therapeutic dose of daunorubicin, preventing the severe side effects of daunorubicin.

Effect of organosulfur compounds on the expression of UDP-glucuronosyltransferase and thyroid hormone level in TCDD-treated rats

In this study, we investigated the effect of organosulfur compounds including, diallyl sulfide (DAS), garlic extract, and dially disulfide (DADS) on inducible expression of UDP-glucuronosyltransferase (UGT1) and thyroid hormone level in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats. We measured UGT1 gene expression in rat liver and lung tissues after treatments. We found that a correlation was found to exist between UGT1 gene expression and active T-4 concentrations. The total concentration of plasma T-4 decreased in TCDD-alone treated male and female rats compared to control animals (TCDD-alone < control). Plasma T-4 concentration in TCDD + DAS, TCDD + garlic extract and TCDD + DADS treated groups were moderately higher than in TCDD alone animals, but lower than control animals. TCDD + DAS, TCDD + garlic extract and TCDD + DADS moderately increased T-4 glucuronidation and moderately reduced total T-4. The nonthyroidal nature of thyroid hormone reduction observed in this study extends the evidence for microsomal enzyme inducers as indirect thyroid tumor promoters in rats. Furthermore, the results of present study suggest protective effects of DAS, garlic extract, or DADS on TCDD-induced changes.