Bufalin derivative BF211 inhibits proteasome activity in human lung cancer cells in vitro by inhibiting β1 subunit expression and disrupting proteasome assembly
文献类型：期刊论文
| 作者 | Pengsun; Feng Lixing; Zhang Dongmei; Liu Miao; Liu Wang; Ml Tian; Wu Wanying ; Jiang Baohong; Yang Min; Hu Lihong
|
| 刊名 | 中国药理学报：英文版
 |
| 出版日期 | 2016 |
| 卷号 | 000期号:007页码:908 |
| 关键词 | 26S蛋白酶体 肺癌细胞 活性肽 衍生物 亚基 体外抑制 蟾酥 A549细胞 |
| ISSN号 | 1671-4083 |
| 英文摘要 | Aim： Bufalin is one of the active components in the traditional Chinese medicine ChanSu that is used to treat arrhythmia, inflammation and cancer. BF211 is a bufalin derivative with stronger cytotoxic activity in cancer cells. The aim of this study was to identify the putative target proteins of BF211 and the signaling pathways in cancer cells. Methods： A549 human lung cancer cells were treated with BF211. A SILAC-based proteomic analysis was used to detect the protein expression profiles of BF211-treated A549 cells. Cellular proteasome activities were examined using fluorogenic peptide substrates, and the binding affinities of BF211 to recombinant proteasome subunit proteins were evaluated using the Biacore assay. The expression levels of proteasome subunits were determined using RT-PCR and Western blotting, and the levels of the integral 26S proteasome were evaluated using native PAGE analysis. Results： The proteomic analysis revealed that 1282 proteins were differentially expressed in BF211-treated A549 cells, and the putative target proteins of BF211 were associated with various cellular functions, including transcription, translation, mRNA splicing, ribosomal protein synthesis and proteasome function. In A549 cells, BF211 （5, 10, and 20 nmol/L） dose-dependently inhibited the enzymatic activities of proteasome. But BF211 displayed a moderate affinity in binding to proteasome 131 subunit and no binding affinity to the 132 and 135 subunits. Moreover, BF211 （0.1, 1, and 10 nmol/L） did not inhibit the proteasome activities in the cell lysates. BF211 （5, 10, and 20 nmol/L） significantly decreased the expression level of proteasome 61 subunit and the levels of integral 26S proteasome in A549 cells. Similarly, knockdown of the β1 subunit with siRNA in A549 cells significantly decreased integral 26S proteasome and proteasome activity. Conclusion： BF211 inhibits proteasome activity in A549 cells by decreasing β1 subunit expression and disrupting proteasome assembly. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/294490]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Pengsun,Feng Lixing,Zhang Dongmei,et al. Bufalin derivative BF211 inhibits proteasome activity in human lung cancer cells in vitro by inhibiting β1 subunit expression and disrupting proteasome assembly[J]. 中国药理学报：英文版,2016,000(007):908. |
| APA | Pengsun.,Feng Lixing.,Zhang Dongmei.,Liu Miao.,Liu Wang.,...&Liu Xuan.(2016).Bufalin derivative BF211 inhibits proteasome activity in human lung cancer cells in vitro by inhibiting β1 subunit expression and disrupting proteasome assembly.中国药理学报：英文版,000(007),908. |
| MLA | Pengsun,et al."Bufalin derivative BF211 inhibits proteasome activity in human lung cancer cells in vitro by inhibiting β1 subunit expression and disrupting proteasome assembly".中国药理学报：英文版 000.007(2016):908. |
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。