Sharma Renu, Vinayak Manjula
Biochemistry and Molecular Biology Laboratory, Center of Advanced Study in Zoology, Banaras Hindu University, Varanasi 221005, India.
Biosci Rep. 2011 Oct;31(5):421-8. doi: 10.1042/BSR20100137.
Cancer development and progression are closely associated with inflammation. NF-κB (nuclear factor κB) provides a mechanistic link between inflammation and cancer, and is a major factor controlling the ability of malignant cells to resist tumour surveillance mechanisms. NF-κB might also regulate tumour angiogenesis and invasiveness and the signalling pathways that mediate its activation provide attractive targets for new chemopreventive and chemotherapeutic approaches. ROS (reactive oxygen species) initiate inflammation by up-regulation of pro-inflammatory cytokines and therefore antioxidants provide a major defence against inflammation. α-Tocopherol is a lipid-soluble antioxidant. In addition to decreasing lipid peroxidation, α-tocopherol may exert intracellular effects. Hence, the aim of this study was to test the effect of α-tocopherol supplementation in cancer prevention via suppression of NF-κB-mediated pro-inflammatory cytokines. α-Tocopherol treatment significantly down-regulates expression, synthesis as well as secretion of pro-inflammatory cytokine IL-6 (interleukin-6) in cancerous mice. It also suppresses NF-κB binding to IL-6 promoter in liver leading to decreased secretion of IL-6 in serum. The regulation of the signalling pathway by α-tocopherol is found apart from its antioxidant capacity to reduce lipid peroxidation. Thus, the present study provides evidence for the hypothesis that besides the powerful free radical scavenging effects, α-tocopherol has genomic effects in down-regulation of pro-inflammatory cytokine and cancer prevention via the NF-κB-dependent pathway.
癌症的发生和发展与炎症密切相关。核因子κB（NF-κB）在炎症和癌症之间建立了一种机制联系，是控制恶性细胞抵抗肿瘤监测机制能力的主要因素。NF-κB还可能调节肿瘤血管生成和侵袭性，介导其激活的信号通路为新的化学预防和化疗方法提供了有吸引力的靶点。活性氧（ROS）通过上调促炎细胞因子引发炎症，因此抗氧化剂是抵御炎症的主要防御手段。α-生育酚是一种脂溶性抗氧化剂。除了减少脂质过氧化作用外，α-生育酚还可能发挥细胞内效应。因此，本研究的目的是通过抑制NF-κB介导的促炎细胞因子来测试补充α-生育酚在癌症预防中的作用。α-生育酚治疗可显著下调癌性小鼠中促炎细胞因子白细胞介素-6（IL-6）的表达、合成及分泌。它还抑制NF-κB与肝脏中IL-6启动子的结合，导致血清中IL-6分泌减少。发现α-生育酚对信号通路的调节与其降低脂质过氧化的抗氧化能力无关。因此，本研究为以下假设提供了证据：除了强大的自由基清除作用外，α-生育酚通过NF-κB依赖途径对促炎细胞因子的下调和癌症预防具有基因组效应。
