Kutuk Ozgur, Basaga Huveyda
Biological Sciences and Bioengineering Program, Sabanci University, 34956 Orhanli, Tuzla, Istanbul, Turkey.
Cytokine. 2004 Mar 7;25(5):229-37. doi: 10.1016/j.cyto.2003.11.007.
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.
Rel/核因子-κB（NF-κB）转录因子参与多个调节增殖、凋亡和细胞生长的靶基因的转录。肿瘤坏死因子α（TNFα）和白细胞介素-1（IL-1）诱导的NF-κB激活途径主要涉及信号体复合物对IκBα的磷酸化和降解，随后NF-κB发生核转位并导致靶基因表达。NF-κB介导细胞死亡与存活之间的平衡，因为大多数具有组成型或诱导型NF-κB激活的癌细胞即使面对如TNFα等强凋亡剂也对凋亡具有抗性。在本研究中，我们证明促炎细胞因子TNFα和IL-1可诱导人宫颈癌HeLa细胞中的NF-κB激活。我们的研究表明，乙酰水杨酸（阿司匹林）通过抑制IκBα和IκBβ的磷酸化和降解，以剂量依赖的方式阻止TNFα和IL-1诱导的NF-κB激活。此外，阿司匹林使HeLa细胞对TNFα诱导的凋亡敏感。这些结果表明，阿司匹林可用于增强基于TNFα的治疗干预措施在癌症治疗中的有效性。
