Aspirin inhibits TNFalpha- and IL-1-induced NF-kappaB activation and sensitizes HeLa cells to apoptosis.

Rel/nuclear factor-kappa B (NF-kappaB) transcription factors are involved in transcription of several target genes that modulate proliferation, apoptosis and cell growth. TNFalpha- and IL-1-induced NF-kappaB activation pathways mainly involve the phosphorylation and degradation of IkappaBalpha by a signalsome complex followed by nuclear translocation of NF-kappaB and target gene expression. NF-kappaB mediates the balance between cell death and survival as most cancer cells that have rather constitutive or inducible activation of NF-kappaB are resistant to apoptosis even by strong apoptotic agents such as TNFalpha. In this study we demonstrate that proinflammatory cytokines TNFalpha and IL-1 induced NF-kappaB activation in human cervical carcinoma HeLa cells. Our studies reveal that acetylsalicylic acid (aspirin) prevents TNFalpha- and IL-1-induced NF-kappaB activation in a dose-dependent manner through inhibition of phosphorylation and degradation of IkappaBalpha and IkappaBbeta. Moreover, aspirin sensitizes HeLa cells to TNFalpha-induced apoptosis. These results suggest that aspirin could be used to potentiate the effectiveness of TNFalpha-based therapeutic interventions in cancer treatment.