Aspirin prevents apoptosis and NF-kappa B activation induced by H2O2 in HeLa cells

Official URL: http://dx.doi.org/10.1080/10715760310001616005

The classical pathway of nuclear factor-kappa B (NF-kappaB) activation by several inducers mainly involves the phosphorylation of IkappaBalpha by a signalsome complex composed of IkappaBalpha kinases (IKKalpha and IKKbeta). However, in some cell types hydrogen peroxide (H2O2) has been shown to activate an alternative pathway that does not involve the classical signalsome activation process. In this study, we demonstrate that H2O2 induced NF-kappaB activation in HeLa cells through phosphorylation and degradation Of IkappaB proteins as shown by immunblot analysis. Our studies reveal that a commonly used non-steroid anti-inflammatory drug, acetylsalicylic acid (aspirin) prevents H2O2-induced NF-kappaB activation in a dose-dependent manner through inhibition of phosphorylation and degradation of IkappaBalpha and IkappaBbeta. Differential staining and DNA fragmentation analysis also show that aspirin preloading of HeLa cells also prevents H2O2-induced apoptosis in a dose-dependent manner with maximum efficiency at 10 mM concentration. Additionally, aspirin effectively prevents caspase-3 and caspase-9 (cysteinyl aspartate-specific proteases) activation by H2O2. These results suggest that NF-kappaB activation is involved in H2O2-induced apoptosis and aspirin may inhibit both processes simultaneously.