DATS suppresses human lung cancer cell growth by causing G2-M phase cell cycle arrest followed by Baxmediated apoptosis. Diallyl sulfide induces cell cycle arrest and apoptosis through the p53, caspase- and mitochondriadependent pathways in HeLa human cervical cancer cells. Allicin induces apoptosis in colon cancer cells. Thiacremonone was isolated as a sulfurcompound from a hot water extract of garlic, and found that this compound could have an anti-cancer effect on colon cancer. Our present data showed that a seventy-two hour treatment of thiacremonone induced cell death of lung cancer cells with an IC50 value of 46 mg/ml in A549 cells, and 42 mg/ml in NCI-H460 cells, respectively. Lung cancer cell growth was significantly decreased by DATS in a concentration- and time-dependent manner with an IC50 of,3.6 mg/ml, and with an IC50 of 7.3 mg/ml by DADS. The IC50 of S-allylcysteine to human metastatic cells was about 5.3 mg/ml at day 3. After treatment for 24 hr, the cell growth of prostate cancer cells with 9 mg/ml sulforaphane was 10.263.1% compared with that in control cells. Even though concentrations of compounds leading cancer cell growth inhibition are different, it depends on the cell type and compounds treated, derived compounds from garlic including thiacremonone have an anticancer effect.

However, exact action mechanisms are still unclear. As PRDX6 scavenge peroxide, such as small H2O2, it supports survival of cancer cells and tumor maintenance. Many studies have demonstrated that PRDX6 promotes invasion and metastasis of a variety of cancer cells including lung, breast, and ovarian cancer cells. PRDX6 is expressed in all major organs, with a particularly high level in the lung. Moreover, PRDX6 was found at higher levels in lung squamous cell carcinoma patients. Overexpression of PRDX6 increased lung cancer cell growth via activity of PRDX6. Thus, targeting PRDX6 by certain compounds could be effective for lung tumor growth inhibition as chemotherapeutics. PRDX6 has dual enzyme activities such as glutathione peroxidase and iPLA2. Glutathione peroxidase promotes cancer cell growth via inhibition of apoptosis and a higher probability or of relapses including lung metastasis and local recurrences. Glutathione peroxidase inhibits cisplatin-induced apoptosis via the down-regulation of Bcl2 in NCI-H460 human lung cancer cells. In the tumor BAY 73-4506 cost tissues, glutathione peroxidase activity was higher than in the tumor-free tissues. Our data showed that decreasing glutathione peroxidase activity in lung cancer cells was associated with lung cancer cell growth inhibition in concentration-dependent manner. Expression of PRDX6 was decreased by thiacremonone in both in vitro and in vivo.

In addition, by the pull-down assay using thiacremonone-agarose bead, we found that thiacremonone bound with recombinant PRDX6 protein or cell lysates containing PRDX6 from human NCI-H460 lung cancer cells, but the binding was not observed in the cell lysates extracted from the cancer cells transfected with C47S-prdx6 mutant plasmid. The cell growth inhibitory effect of thiacremonone was also significantly abolished in cells transfected C47S-prdx6 mutant plasmid.