Dietary apigenin potentiates the inhibitory effect of interferon-alpha on cancer cell viability through inhibition of 26S proteasome-mediated interferon receptor degradation
文献类型：期刊论文
| 作者 | He, YJ; Yang, LJ; Li, S; Wang, F (reprint author), Chinese Acad Sci, Chengdu Inst Biol, 9 Sect 4 Renmin South Rd, Chengdu 610041, Peoples R China.; Wang, F; Shen, XF; Liu, HW; Huang, JM; Wang, P |
| 刊名 | FOOD & NUTRITION RESEARCH
 |
| 出版日期 | 2016 |
| 卷号 | 60页码:31288（1-12） |
| 关键词 | Apigenin Interferon Proteasome Stat Ubiquitination |
| DOI | 10.3402/fnr.v60.31288 |
| 产权排序 | 1 |
| 文献子类 | Article |
| 英文摘要 | Background: Type I interferons (IFN-alpha/beta) have broad and potent immunoregulatory and antiproliferative activities. However, it is still known whether the dietary flavonoids exhibit their antiviral and anticancer properties by modulating the function of type I IFNs. Objective: This study aimed at determining the role of apigenin, a dietary plant flavonoid abundant in common fruits and vegetables, on the type I IFN-mediated inhibition of cancer cell viability. Design: Inhibitory effect of apigenin on human 26S proteasome, a known negative regulator of type I IFN signaling, was evaluated in vitro. Molecular docking was conducted to know the interaction between apigenin and subunits of 26S proteasome. Effects of apigenin on JAK/STAT pathway, 26S proteasome-mediated interferon receptor stability, and cancer cells viability were also investigated. Results: Apigenin was identified to be a potent inhibitor of human 26S proteasome in a cell-based assay. Apigenin inhibited the chymotrypsin-like, caspase-like, and trypsin-like activities of the human 26S proteasome and increased the ubiquitination of endogenous proteins in cells. Results from computational modeling of the potential interactions of apigenin with the chymotrypsin site (beta 5 subunit), caspase site (beta 1 subunit), and trypsin site (beta 2 subunit) of the proteasome were consistent with the observed proteasome inhibitory activity. Apigenin enhanced the phosphorylation of signal transducer and activator of transcription proteins (STAT1 and STAT2) and promoted the endogenous IFN-alpha-regulated gene expression. Apigenin inhibited the IFN-alpha-stimulated ubiquitination and degradation of type I interferon receptor 1 (IFNAR1). Apigenin also sensitized the inhibitory effect of IFN-alpha on viability of cervical carcinoma HeLa cells. Conclusion: These results suggest that apigenin potentiates the inhibitory effect of IFN-alpha on cancer cell viability by activating JAK/STAT signaling pathway through inhibition of 26S proteasome-mediated IFNAR1 degradation. This may provide a novel mechanism for increasing the efficacy of IFN-alpha/beta. |
| 学科主题 | Food Science & Technology ; Nutrition & Dietetics |
| 语种 | 英语 |
| 资助机构 | National Natural Science Foundation of China [1372214, 91413108, 21561142003] ; National Natural Science Foundation of China [1372214, 91413108, 21561142003] ; Sichuan Youth Science & Technology Foundation [2014JQ0028] ; Sichuan Youth Science & Technology Foundation [2014JQ0028] ; West Light Foundation of the Chinese Academy of Sciences ; West Light Foundation of the Chinese Academy of Sciences ; Research Foundation of State General Administration of The People's Republic of China for Quality Supervision and Inspection and Quarantine [2015IK180] ; Research Foundation of State General Administration of The People's Republic of China for Quality Supervision and Inspection and Quarantine [2015IK180] ; National Natural Science Foundation of China [1372214, 91413108, 21561142003] ; National Natural Science Foundation of China [1372214, 91413108, 21561142003] ; Sichuan Youth Science & Technology Foundation [2014JQ0028] ; Sichuan Youth Science & Technology Foundation [2014JQ0028] ; West Light Foundation of the Chinese Academy of Sciences ; West Light Foundation of the Chinese Academy of Sciences ; Research Foundation of State General Administration of The People's Republic of China for Quality Supervision and Inspection and Quarantine [2015IK180] ; Research Foundation of State General Administration of The People's Republic of China for Quality Supervision and Inspection and Quarantine [2015IK180] |
| 源URL | [http://210.75.237.14/handle/351003/28214]  |
| 专题 | 成都生物研究所_天然产物研究 |
| 通讯作者 | Wang, F (reprint author), Chinese Acad Sci, Chengdu Inst Biol, 9 Sect 4 Renmin South Rd, Chengdu 610041, Peoples R China. |
| 推荐引用方式 GB/T 7714 | He, YJ,Yang, LJ,Li, S,et al. Dietary apigenin potentiates the inhibitory effect of interferon-alpha on cancer cell viability through inhibition of 26S proteasome-mediated interferon receptor degradation[J]. FOOD & NUTRITION RESEARCH,2016,60:31288（1-12）. |
| APA | He, YJ.,Yang, LJ.,Li, S.,Wang, F .,Wang, F.,...&Wang, P.(2016).Dietary apigenin potentiates the inhibitory effect of interferon-alpha on cancer cell viability through inhibition of 26S proteasome-mediated interferon receptor degradation.FOOD & NUTRITION RESEARCH,60,31288（1-12）. |
| MLA | He, YJ,et al."Dietary apigenin potentiates the inhibitory effect of interferon-alpha on cancer cell viability through inhibition of 26S proteasome-mediated interferon receptor degradation".FOOD & NUTRITION RESEARCH 60(2016):31288（1-12）. |
入库方式： OAI收割
来源：成都生物研究所
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。