Aspirin inhibits TNFα- and IL-1-induced NF-κB 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 NFkappaB are resistant to apoptosis even by strong apoptotic agents such as TNFalpha. In this study we demonstrate that proinfammatory 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. (C) 2004 Elsevier Ltd. All rights reserved.