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

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Kutuk O, Basaga H

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

Cytokine. 2004 Mar 7;25(5):229-37. doi: 10.1016/j.cyto.2003.11.007.

PubMed ID

15036249 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Acetylsalicylic acid	Tumor necrosis factor-inducible gene 6 protein	Protein	Humans	Unknown	Inhibitor Downregulator	Details