Chemopreventive agents induce suppression of nuclear factor-κB leading to chemosensitization
Chemopreventive agents induce suppression of nuclear factor-κB leading to chemosensitization
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DOI：
10.1111/j.1749-6632.2002.tb04671.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Aggarwal, BB
中科院分区：
文献类型：
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作者：
Bharti, AC;Aggarwal, BB
核因子-kappaB(NF-kappaB)是一种转录因子，通常以p50、p65和1KBalpha亚基组成的非活性异源三聚体存在于细胞质中。当被激活时，核因子-kappaB以p50-p65异源二聚体的形式转移到细胞核。该因子调节各种基因的表达，这些基因控制着细胞凋亡、病毒复制、肿瘤发生、各种自身免疫性疾病和炎症。由于几个原因，核因子-kappaB与癌症的发生有关。首先，各种致癌物和肿瘤促进剂已被证明能激活核因子-kappaB。第二，核因子-kappaB的激活被证明可以阻止细胞凋亡和促进细胞增殖。第三，肿瘤微环境可诱导核因子-kappaB的激活。第四，核因子-kappaB在肿瘤细胞中广泛表达。第五，核因子-kappaB的激活诱导对化疗药物的耐药。第六，参与肿瘤启动、促进和转移的几个基因受核因子-kappaB的调控。第七，已发现多种化学预防药物可下调核因子-kappaB的激活。所有这些观察表明，核因子-kappaB可以介导肿瘤的发生，因此可以作为化学预防和癌症治疗的靶点。抑制核因子-kappaB活性的药物可以在体内抑制与癌症发生和肿瘤发生有关的基因的表达。
Nuclear factor-kappaB (NF-kappaB), a transcription factor, is present normally in the cytoplasm as an inactive heterotrimer consisting of p50, p65, and 1KBalpha subunits. When activated, NF-kappaB translocates to the nucleus as a p50-p65 heterodimer. This factor regulates the expression of various genes that control apoptosis, viral replication, tumorigenesis, various autoimmune diseases, and inflammation. NF-kappaB has been linked to the development of carcinogenesis for several reasons. First, various carcinogens and tumor promoters have been shown to activate NF-kappaB. Second, activation of NF-kappaB has been shown to block apoptosis and promote proliferation. Third, the tumor microenvironment can induce NF-kappaB activation. Fourth, constitutive expression of NF-kappaB is frequently found in tumor cells. Fifth, NF-kappaB activation induces resistance to chemotherapeutic agents. Sixth, several genes involved in tumor initiation, promotion, and metastasis are regulated by NF-kappaB. Seventh, various chemopreventive agents have been found to down-regulate the NF-kappaB activation. All these observation suggest that NF-kappaB could mediate tumorigenesis and thus can be used as a target for chemoprevention and for the treatment of cancer. Agents that suppress NF-kappaB activation can suppress the expression of genes involved in carcinogenesis and tumorigenesis in vivo.