6-Hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside potentiates the anti-proliferative effect of interferon alpha/beta by promoting activation of the JAK/STAT signaling by inhibiting SOCS3 in hepatocellular carcinoma cells | |
Wonganan, O; He, YJ; Shen, XF; Wongkrajang, K; Suksamrarn, A; Zhang, GL; Wang, F; Wang, F (reprint author), Chinese Acad Sci, Chengdu Inst Biol, Key Lab Nat Med & Clin Translat, Chengdu 610041, Sichuan, Peoples R China. | |
刊名 | TOXICOLOGY AND APPLIED PHARMACOLOGY |
2017 | |
卷号 | 336页码:31-39 |
关键词 | Kaempferol Glucopyranoside Saussurea Stella Interferon Jak/stat Socs3 |
DOI | 10.1016/j.taap.2017.10.004 |
产权排序 | 1 |
文献子类 | Article |
英文摘要 | Suppressor of cytokine signaling 3 (SOCS3) is a key negative regulator of type I interferon (IFN alpha/beta) signaling. Inhibition of SOCS3 by small molecules may be a new strategy to enhance the efficacy of type I IFN and reduce its side effects. We established a cell-based screening assay using human hepatoma HepG2 cells stably transfected with a plasmid wherein the luciferase reporter activity was propelled by interferon alpha-stimulated response element (ISRE), which is a motif specifically recognized by type I IFN-induced activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. After screening our chemical library, 6-hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside (K6G) was identified to be a potent activator of type I IFN with EC50 value of 3.33 +/- 0.04 mu M. K6G enhanced the phosphorylation of JAK1, Tyk2, and STAT1/2 but decreased the phosphorylation of STAT3. K6G also promoted endogenous IFN-alpha-regulated genes expression. More interestingly, K6G significantly decreased the expression of SOCS3 without affecting the expression of SOCS1. Furthermore, K6G enhanced the anti-proliferative effect of IFN-alpha on hepatocellular carcinoma (HCC) cells. These results suggested that K6G potentiated the inhibitory effect of IFN-alpha on HCC cell proliferation through activation of the JAK/STAT signaling pathway by inhibiting SOCS3 expression. K6G warrants further investigation as a novel therapeutic method to enhance the efficacy of IFN-alpha/beta. |
学科主题 | Pharmacology & Pharmacy ; Toxicology |
项目编号 | 天然药物和临床转化实验室 |
语种 | 英语 |
资助机构 | This work was supported by the National Natural Science Foundation of China (No. 21561142003, 21672207), Science & Technology Department of Sichuan Province (No. 2016HH0073, 2016JZ0022), CAS-TWAS President's PhD Fellowship Program, Chinese Academy of Sciences President's International Fellowship Initiative (No. 2015PB061), and the National New Drug Innovation Major Project of China (2017ZX09101003-001-006). Support from The Thailand Research Fund (No. DBG5980003) is gratefully acknowledged. ; National Natural Science Foundation of China [21561142003, 21672207] ; This work was supported by the National Natural Science Foundation of China (No. 21561142003, 21672207), Science & Technology Department of Sichuan Province (No. 2016HH0073, 2016JZ0022), CAS-TWAS President's PhD Fellowship Program, Chinese Academy of Sciences President's International Fellowship Initiative (No. 2015PB061), and the National New Drug Innovation Major Project of China (2017ZX09101003-001-006). Support from The Thailand Research Fund (No. DBG5980003) is gratefully acknowledged. ; National Natural Science Foundation of China [21561142003, 21672207] ; Science & Technology Department of Sichuan Province [2016HH0073, 2016JZ0022] ; Science & Technology Department of Sichuan Province [2016HH0073, 2016JZ0022] ; CAS-TWAS President's PhD Fellowship Program, Chinese Academy of Sciences President's International Fellowship Initiative [2015PB061] ; CAS-TWAS President's PhD Fellowship Program, Chinese Academy of Sciences President's International Fellowship Initiative [2015PB061] ; National New Drug Innovation Major Project of China [2017ZX09101003-001-006] ; National New Drug Innovation Major Project of China [2017ZX09101003-001-006] ; Thailand Research Fund [DBG5980003] ; Thailand Research Fund [DBG5980003] ; This work was supported by the National Natural Science Foundation of China (No. 21561142003, 21672207), Science & Technology Department of Sichuan Province (No. 2016HH0073, 2016JZ0022), CAS-TWAS President's PhD Fellowship Program, Chinese Academy of Sciences President's International Fellowship Initiative (No. 2015PB061), and the National New Drug Innovation Major Project of China (2017ZX09101003-001-006). Support from The Thailand Research Fund (No. DBG5980003) is gratefully acknowledged. ; National Natural Science Foundation of China [21561142003, 21672207] ; This work was supported by the National Natural Science Foundation of China (No. 21561142003, 21672207), Science & Technology Department of Sichuan Province (No. 2016HH0073, 2016JZ0022), CAS-TWAS President's PhD Fellowship Program, Chinese Academy of Sciences President's International Fellowship Initiative (No. 2015PB061), and the National New Drug Innovation Major Project of China (2017ZX09101003-001-006). Support from The Thailand Research Fund (No. DBG5980003) is gratefully acknowledged. ; National Natural Science Foundation of China [21561142003, 21672207] ; Science & Technology Department of Sichuan Province [2016HH0073, 2016JZ0022] ; Science & Technology Department of Sichuan Province [2016HH0073, 2016JZ0022] ; CAS-TWAS President's PhD Fellowship Program, Chinese Academy of Sciences President's International Fellowship Initiative [2015PB061] ; CAS-TWAS President's PhD Fellowship Program, Chinese Academy of Sciences President's International Fellowship Initiative [2015PB061] ; National New Drug Innovation Major Project of China [2017ZX09101003-001-006] ; National New Drug Innovation Major Project of China [2017ZX09101003-001-006] ; Thailand Research Fund [DBG5980003] ; Thailand Research Fund [DBG5980003] |
内容类型 | 期刊论文 |
源URL | [http://210.75.237.14/handle/351003/29206] |
专题 | 成都生物研究所_天然产物研究 |
通讯作者 | Zhang, GL; Wang, F (reprint author), Chinese Acad Sci, Chengdu Inst Biol, Key Lab Nat Med & Clin Translat, Chengdu 610041, Sichuan, Peoples R China. |
推荐引用方式 GB/T 7714 | Wonganan, O,He, YJ,Shen, XF,et al. 6-Hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside potentiates the anti-proliferative effect of interferon alpha/beta by promoting activation of the JAK/STAT signaling by inhibiting SOCS3 in hepatocellular carcinoma cells[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2017,336:31-39. |
APA | Wonganan, O.,He, YJ.,Shen, XF.,Wongkrajang, K.,Suksamrarn, A.,...&Wang, F .(2017).6-Hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside potentiates the anti-proliferative effect of interferon alpha/beta by promoting activation of the JAK/STAT signaling by inhibiting SOCS3 in hepatocellular carcinoma cells.TOXICOLOGY AND APPLIED PHARMACOLOGY,336,31-39. |
MLA | Wonganan, O,et al."6-Hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside potentiates the anti-proliferative effect of interferon alpha/beta by promoting activation of the JAK/STAT signaling by inhibiting SOCS3 in hepatocellular carcinoma cells".TOXICOLOGY AND APPLIED PHARMACOLOGY 336(2017):31-39. |
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