論文 - 詳細
| RRC ID | 19606 |
|---|---|
| 著者 | Auyeung KK, Cho CH, Ko JK. |
| タイトル | A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID-activated gene. |
| ジャーナル | Int J Cancer |
| Abstract |
Astragalus membranaceus has been used to ameliorate the side effects of antineoplastic drugs because of its immunomodulating nature. We had recently demonstrated that total Astragalus saponins (AST) possess anticarcinogenic and proapoptotic properties in human colon cancer cells and tumor xenograft. In this study, we identified NSAID-activated gene (NAG-1) as a potential molecular target of AST. The growth-inhibitory and proapoptotic effects of AST were assessed in a panel of human cancer cell lines. Hoechst 33342 nuclear staining, Annexin V-FITC/propidium iodide staining, Western immunoblotting, real-time PCR, luciferase reporter assay and electrophoretic mobility shift assay were conducted to determine the association of NAG-1 and related transcription factors with AST during its regulation of apoptotic activities. Moreover, the combined proapoptotic and NAG-1 promoting activities of AST and/or inhibitors of the PI3K-Akt pathway were also examined. AST caused overexpression of NAG-1, leading to PARP cleavage and apoptosis. The induction of NAG-1 promoter activity by the drug was associated with increased gene expression, in addition to prior increase in Egr-1 expression and DNA binding activity. AST-induced NAG-1 activation was intensified when PI3K inhibitor LY294002 or Akt inhibitor was co-treated and reversed by NAG-1 siRNA transfection. Nevertheless, the extent of NAG-1 induction could not be altered by the ERK inhibitor PD98059. Our results indicate that NAG-1 is a potential molecular target of AST in its antitumorigenic and proapoptotic actions, which would have additive effects when used along with PI3K-Akt inhibitors. The information obtained could facilitate future development of a novel target-specific chemotherapeutic agent with known molecular pathway. |
| 巻・号 | 125(5) |
| ページ | 1082-91 |
| 公開日 | 2009-9-1 |
| DOI | 10.1002/ijc.24397 |
| PMID | 19384947 |
| MeSH | Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Antineoplastic Agents / pharmacology* Astragalus Plant / chemistry* Blotting, Western Early Growth Response Protein 1 / metabolism Electrophoretic Mobility Shift Assay Gene Expression Regulation, Neoplastic / drug effects* Growth Differentiation Factor 15 / genetics* Growth Differentiation Factor 15 / metabolism Humans Luciferases / metabolism Promoter Regions, Genetic / genetics Proto-Oncogene Proteins c-akt / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Small Interfering / pharmacology Reverse Transcriptase Polymerase Chain Reaction Saponins / pharmacology* Transcriptional Activation* Transfection Tumor Cells, Cultured |
| IF | 5.145 |
| 引用数 | 56 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |