KO-202125, a sauristolactam derivate, induces apoptosis to prevent KB human oral squamous carcinoma cells through inhibition of cyclooxygenase-2 expression.

In a previous study, we demonstrated that cyclooxygenase-2 (COX-2) is overexpressed in Korean patients having oral cancer. The goal of this study was to study whether KO-202125 (KO), a sauristolactam derivative in KB human oral squamous carcinoma cells, inhibits the activity of COX-2 enzyme and induces apoptotic cell death. In this study, it was shown that KO inhibited COX-2 mRNA and protein and its catalytic activity (prostaglandin E2), but not COX-1. The antiproliferative effect of KO on KB cells was also examined. The results showed that KO significantly decreased the number of viable cells and showed morphological changes in a concentration-dependent manner. The decrease in cell number was associated with apoptotic cell death evidenced by cleaved poly ADP ribose polymerase (PARP), nuclear fragmentation, sub-G1 population and annexin V positivity. Interestingly, KO is more potent than celecoxib, which is a well-known selective COX-2 inhibitor, although more studies are needed to prove it. Altogether, these results show that KO can act as a potent antioral cancer drug candidate by regulating COX-2 activity.