Inhibition of cyclooxygenase-2 by diallyl sulfides (DAS) in HEK 293T cells

Cyclooxygenase (COX) is involved in modulating inflammatory response through the synthesis of prostaglandins. The inducible isoform of the enzyme, COX-2, is overexpressed in some malignant and premalignant lesions. Several preclinical and clinical studies have reported COX-2 inhibition as an effective strategy for chemoprevention. Nonsteroidal anitinflammatory drugs (NASIDs) such as celecoxib, are the most widely investigated COX-2 inhibitors. The oil-soluble diallyl sulfides (DAS) include monosulfides (DAMS), disulfides (DADS) and trisulfides (DATS). They were found to be effective against canine and human tumors, the mechanism of which remains unresolved. We attempted a comparative evaluation of the antiproliferative effect of DAS in HEK 293T cells. The cells were treated with increasing concentrations of DAMS, DADS and DATS. There were significant differences between the IC50 values of DAMS, DADS and DATS. RT-PCR was performed and the expression of COX-2 was compared with that of b actin. DATS inhibited COX-2 gene expression significantly stronger than DAMS and DADS. The data are suggestive of antineoplastic effect of DAS, mediated by controlling COX-2 expression.