Regulation of constitutive and induced NF-kappaB activation in malignant melanoma cells by capsaicin modulates interleukin-8 production and cell proliferation.
Regulation of constitutive and induced NF-kappaB activation in malignant melanoma cells by capsaicin modulates interleukin-8 production and cell proliferation.
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辣椒素调节恶性黑色素瘤细胞中的组成型和诱导型 NF-κB 激活，从而调节 IL-8 的产生和细胞增殖。
DOI：
10.1089/10799900252952217
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Singh,RakeshK
中科院分区：
文献类型：
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作者：
Patel,PrabhudasS;Varney,MichelleL;Dave,BhavanaJ;Singh,RakeshK
在本研究中，我们证明了白细胞介素1β（IL-1β）介导的和肿瘤坏死因子-α（TNF-α）介导的IL-8表达的上调， 人恶性黑色素瘤细胞通过核因子-κB（NF-κB）的活化来调节。加入辣椒素（8-甲基-N-香草基-6-壬烯酰胺），一种已知的NF-κB抑制剂， 导致黑色素瘤细胞中组成型以及IL-1β诱导和TNF-α诱导的IL-8表达的抑制。IL-8表达的抑制呈浓度依赖性 辣椒素的剂量和疗程此外，从黑色素瘤细胞的核提取物的电泳迁移率变动分析（EMSA）显示NF-κB的组成性激活，并且激活了NF-κB的表达。 蛋白1（AP-1），其在用IL-1β处理后上调。用辣椒素处理黑色素瘤细胞抑制了组成型和IL-1β诱导的NF-κB的活化， 而AP-1则没有，导致IL-8表达的抑制。此外，辣椒素处理的黑色素瘤细胞中IL-8表达的下调导致体外细胞增殖的抑制。这些 结果表明，组成型和诱导型NF-κB活化调节黑素瘤细胞中IL-8的表达。恶性肿瘤组织中NF-κB的组成性和诱导性活化下调 黑色素瘤细胞导致IL-8产生和体外细胞增殖的抑制。
In the present study, we demonstrate that upregulation of interleukin-1β(IL-1β)-mediated and tumor necrosis factor-α(TNF-α)-mediated IL-8 expression in human malignant melanoma cells is modulated by the activation of nuclear factor-κB (NF-κB). Addition of capsaicin (8-methyl-N-vanillyl-6-nonenamide), a known inhibitor of NF-κB, resulted in the inhibition of constitutive as well as IL-1β-induced and TNF-α-induced IL-8 expression in melanoma cells. The inhibition of IL-8 expression was dependent on the concentration of capsaicin and duration of treatment. Further, electrophoretic mobility shift assay (EMSA) of nuclear extracts from melanoma cells showed a constitutive activation of NF-κB and activated protein 1 (AP-1), which was upregulated following treatment with IL-1β. Treatment of melanoma cells with capsaicin inhibited activation of constitutive and IL-1β-induced NF-κB, but not AP-1, leading to inhibition of IL-8 expression. Further, downregulation of IL-8 expression in capsaicin-treated melanoma cells resulted in inhibition ofin vitrocell proliferation. These results demonstrate that constitutive and induced NF-κB activation regulates IL-8 expression in melanoma cells. Downregulation of constitutive and induced NF-κB activation in malignant melanoma cells leads to inhibition of IL-8 production andin vitrocell proliferation.