Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-kappa B signaling pathway with distinct mechanisms
文献类型：期刊论文
| 作者 | Peng, Yan-min1; Zheng, Jian-bin2; Zhou, Yu-bo1 ; Li, Jia1
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2013-07 |
| 卷号 | 34期号:7页码:939-950 |
| 关键词 | curcumin P1 anticancer agent high-throughput screen NF-kappa B HeLa cell mitochondria ROS |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2013.2 |
| 文献子类 | Article |
| 英文摘要 | Aim: Curcumin has shown promising anticancer activity, which relies on its inhibition on NF-kappa B pathway. In this study, we characterized the pharmacological profile of a novel curcumin analog P1 and elucidate the related mechanisms. Methods: HEK293/NF-kappa B cells, stably transfected with an NF-kappa B-responsive luciferase reporter plasmid, were generated for high-throughput 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-kappa B pathway. Its IC50 value in inhibition of TNF-alpha-induced NF-kappa B activation was 0.8 mu mol/L, whereas its IC50 values in inhibiting the growth of A549 and HeLa cells were 1.24 and 0.69 mu mol/L, respectively, which was 20- to 30-fold more potent than curcumin. The inhibition of P1 on the NF-kappa B pathway was further addressed in HeLa cells. The compound up to 10 mu mol/L did not affect the binding of NF-kappa B to DNA, but markedly inhibited NF-kappa B nuclear translocation, I kappa B degradation and I kappa B kinase phosphorylation. The compound (1 and 3 mu mol/L) concentration-dependently induced ROS generation, whereas curcumin up to 20 mu mol/L had no effect. P1-induced ROS generation was mainly localized in mitochondria, and reversed by NAC. Moreover, the compound significantly enhanced TNF-alpha-induced apoptosis. Conclusion: P1 is a novel curcumin analog with potent anticancer activities, which exerts a distinct inhibition on the NF-kappa B pathway. |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; REGULATED GENE-PRODUCTS ; PANCREATIC-CANCER ; TNF-ALPHA ; OXIDATIVE STRESS ; TUMOR-CELLS ; APOPTOSIS ; PROLIFERATION ; SUPPRESSION ; EXPRESSION |
| 资助项目 | National Natural Science Foundation of China[91029716] ; National Natural Science Foundation of China[81021062] ; National Natural Science Foundation of China[81072667] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4874888 |
| WOS记录号 | WOS:000321332700010 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277556]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Zhou, Yu-bo |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Peng, Yan-min,Zheng, Jian-bin,Zhou, Yu-bo,et al. Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-kappa B signaling pathway with distinct mechanisms[J]. ACTA PHARMACOLOGICA SINICA,2013,34(7):939-950. |
| APA | Peng, Yan-min,Zheng, Jian-bin,Zhou, Yu-bo,&Li, Jia.(2013).Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-kappa B signaling pathway with distinct mechanisms.ACTA PHARMACOLOGICA SINICA,34(7),939-950. |
| MLA | Peng, Yan-min,et al."Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-kappa B signaling pathway with distinct mechanisms".ACTA PHARMACOLOGICA SINICA 34.7(2013):939-950. |
入库方式： OAI收割
来源：上海药物研究所
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