Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-kB signaling pathway with distinct mechanisms
文献类型：期刊论文
| 作者 | Peng Yanmin2; Zheng Jianbin1; Zhou Yubo2 ; Li Jia2
|
| 刊名 | Acta Pharmacologica Sinica
 |
| 出版日期 | 2013 |
| 卷号 | 34期号:7页码:939 |
| 关键词 | curcumin P1 anticancer agent high-throughput screen NF-kB HeLa cell mitochondria ROS |
| ISSN号 | 1671-4083 |
| 英文摘要 | Aim: Curcumin has shown promising anticancer activity, which relies on its inhibition on NF-kB pathway. In this study, we characterized the pharmacological profile of a novel curcumin analog P1 and elucidate the related mechanisms. Methods: HEK293/NF-kB cells, stably transfected with an NF-KB-responsive luciferase reporter plasmid, were generated for highthroughput screen (HTS). Eight cancer cell lines, including PC3, COLO 205, HeLa cells etc. were tested. Cell viability was assessed using the sulforhodamine B (SRB) assays. Cell apoptosis was evaluated using FACS, immunocytochemistry, and Western blotting. H_2-DCFDA and MitoSOX Red were used to detect cellular and mitochondrial reactive oxygen species (ROS). The mitochondrial function was evaluated using mitochondrial oxygen consumption assay. Results: P1, a tropinone curcumin, was found in HTS targeting the NF-kB pathway. Its IC_(50) value in inhibition of TNF-α-induced NF-kB activation was 0.8 pmol/L, whereas its IC_(50) values in inhibiting the growth of A549 and HeLa cells were 1.24 and 0.69 μmol/L, respectively, which was 20- to 30-fold more potent than curcumin. The inhibition of P1 on the NF-kB pathway was further addressed in HeLa cells. The compound up to 10 μmol/L did not affect the binding of NF-kB to DNA, but markedly inhibited NF-kB nuclear translocation, IkB degradation and IkB kinase phosphorylation. The compound (1 and 3 μmol/L) concentration-dependently induced ROS generation, whereas curcumin up to 20 pmol/L had no effect. Pl-induced ROS generation was mainly localized in mitochondria, and reversed by NAC. Moreover, the compound significantly enhanced TNF-α-induced apoptosis. Conclusion: P1 is a novel curcumin analog with potent anticancer activities, which exerts a distinct inhibition on the NF-kB pathway. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/293748]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.华东理工大学 2.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Peng Yanmin,Zheng Jianbin,Zhou Yubo,et al. Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-kB signaling pathway with distinct mechanisms[J]. Acta Pharmacologica Sinica,2013,34(7):939. |
| APA | Peng Yanmin,Zheng Jianbin,Zhou Yubo,&Li Jia.(2013).Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-kB signaling pathway with distinct mechanisms.Acta Pharmacologica Sinica,34(7),939. |
| MLA | Peng Yanmin,et al."Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-kB signaling pathway with distinct mechanisms".Acta Pharmacologica Sinica 34.7(2013):939. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。