Esculetin Neutralises Cytotoxicity of t-BHP but Not of H(2)O(2) on Human Leukaemia NB4 Cells

The coumarin esculetin shows antioxidant action on some cell types, both by scavenging ROS and by decreasing ROS production. We have previously demonstrated the induction of apoptosis by esculetin on NB4 human leukaemia cells by an ill-defined mechanism related to ROS levels. In this work, we analyze the effect of the simultaneous treatment with esculetin and two oxidants to observe the early events in the mechanism of esculetin-induced apoptosis. Our results show that, from the early time of 15 min, esculetin acts synergistically with H(2)O(2) to decrease cell viability and metabolic activity and to increase apoptosis in NB4 cells. In contrast, the early oxidative effects of t-BHP are neutralised by esculetin, protecting human leukaemia NB4 cells from apoptosis. Esculetin seems to restrict the increase in peroxides caused by H(2)O(2) or t-BHP in the time interval analyzed. These results contribute to a better understanding of the cytotoxic effect caused by esculetin on NB4 cells. At the same time, the early neutralisation of exogenous oxidants could be of interest to prevent diseases related to oxidative stress imbalance.