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.
Kutuk
Ozgur
O
Biological Sciences and Bioengineering Program, Sabanci University, 34956 Orhanli, Tuzla, Istanbul, Turkey.
Basaga
Huveyda
H
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020672:I-kappa B Proteins; D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D001241:Aspirin