Luteolin sensitizes the antiproliferative effect of interferon alpha/beta by activation of Janus kinase/signal transducer and activator of transcription pathway signaling through protein kinase A-mediated inhibition of protein tyrosine phosphatase SHP-2 in cancer cells
文献类型：期刊论文
| 作者 | Tai, Zhengfu ; Lin, Yuan ; He, Yujiao ; Huang, Junmei ; Guo, Jiajia ; Yang, Lijuan ; Zhang, Guolin ; Wang, Fei |
| 刊名 | CELLULAR SIGNALLING
 |
| 出版日期 | 2014 |
| 卷号 | 26期号:3页码:619-628 |
| 关键词 | Luteolin Interferon Phosphodiesterase PKA SHP-2 |
| 产权排序 | 1 |
| 通讯作者 | Zhang, GL (reprint author), Chinese Acad Sci, Chengdu Inst Biol, PO 416, Chengdu 610041, Peoples R China. |
| 合作状况 | 其它 |
| 英文摘要 | New negative regulators of interferon (IFN) signaling, preferably with tissue specificity, are needed to develop therapeutic means to enhance the efficacy of type I IFNs (IFN-alpha/beta) and reduce their side effects. We conducted cell-based screening for IFN signaling enhancer and discovered that luteolin, a natural flavonoid, sensitized the antiproliferative effect of IFN-alpha in hepatoma HepG2 cells and cervical carcinoma HeLa cells. Luteolin promoted IFN-beta-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation by enhancing the phosphorylation of Jak1, Tyk2, and STAT1/2, thereby promoting STAT1 accumulation in the nucleus and endogenous IFN-alpha-regulated gene expression. Of interest, inhibition of phosphodiesterase (PDE) abolished the effect of IFN-beta and luteolin on STATI phosphorylation. Luteolin also increased the cAMP-degrading activity of PDE bound with type I interferon receptor 2 (IFNAR2) and decreased the intracellular cAMP level, indicating that luteolin may act on the JAK/STAT pathway via PDE. Protein kinase A (PKA) was found to negatively regulate IFN-beta-induced JAK/STAT signaling, and its inhibitory effect was counteracted by luteolin. Pull-down and immunoprecipitation assays revealed that type II PICA interacted with IFNAR2 via the receptor for activated C-kinase 1 (RACK-1), and such interaction was inhibited by luteolin. Src homology domain 2 containing tyrosine phosphatase-2 (SHP-2) was further found to mediate the inhibitory effect of PKA on the JAK/STAT pathway. These data suggest that PKA/PDE-mediated cAMP signaling, integrated by RACK-I to IFNAR2, may negatively regulate IFN signaling through SHP-2. Inhibition of this signaling may provide a new way to sensitize the efficacy of IFN-alpha/beta. (C) 2013 Elsevier Inc. All rights reserved. |
| 学科主题 | Cell Biology |
| 收录类别 | SCI |
| 语种 | 英语 |
| 公开日期 | 2016-02-26 |
| 源URL | [http://210.75.237.14/handle/351003/26695]  |
| 专题 | 成都生物研究所_天然产物研究 |
| 推荐引用方式 GB/T 7714 | Tai, Zhengfu,Lin, Yuan,He, Yujiao,et al. Luteolin sensitizes the antiproliferative effect of interferon alpha/beta by activation of Janus kinase/signal transducer and activator of transcription pathway signaling through protein kinase A-mediated inhibition of protein tyrosine phosphatase SHP-2 in cancer cells[J]. CELLULAR SIGNALLING,2014,26(3):619-628. |
| APA | Tai, Zhengfu.,Lin, Yuan.,He, Yujiao.,Huang, Junmei.,Guo, Jiajia.,...&Wang, Fei.(2014).Luteolin sensitizes the antiproliferative effect of interferon alpha/beta by activation of Janus kinase/signal transducer and activator of transcription pathway signaling through protein kinase A-mediated inhibition of protein tyrosine phosphatase SHP-2 in cancer cells.CELLULAR SIGNALLING,26(3),619-628. |
| MLA | Tai, Zhengfu,et al."Luteolin sensitizes the antiproliferative effect of interferon alpha/beta by activation of Janus kinase/signal transducer and activator of transcription pathway signaling through protein kinase A-mediated inhibition of protein tyrosine phosphatase SHP-2 in cancer cells".CELLULAR SIGNALLING 26.3(2014):619-628. |
入库方式： OAI收割
来源：成都生物研究所
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