Aspirin inhibits TNF alpha- and IL-1-induced NF-kappa B activation and sensitizes HeLa cells to apoptosis

Official URL: http://dx.doi.org/10.1016/j.cyto.2003.11.007

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