論文 - 詳細
| RRC ID | 67289 |
|---|---|
| 著者 | Wong CP, Seki A, Horiguchi K, Shoji T, Arai T, Nugroho AE, Hirasawa Y, Sato F, Kaneda T, Morita H. |
| タイトル | Bisleuconothine A Induces Autophagosome Formation by Interfering with AKT-mTOR Signaling Pathway. |
| ジャーナル | J Nat Prod |
| Abstract |
We have previously reported that bisleuconothine A (Bis-A), a novel bisindole alkaloid isolated from Leuconotis griffithii, showed cytostatic activity in several cell lines. In this report, the mechanism of Bis-A-induced cytostatic activity was investigated in detail using A549 cells. Bis-A did not cause apoptosis, as indicated by analysis of annexin V and propidium iodide staining. Expression of all tested apoptosis-related proteins was also unaffected by Bis-A treatment. Bis-A was found to increase LC3 lipidation in MCF7 cells as well as A549 cells, suggesting that Bis-A cytostatic activity may be due to induction of autophagy. Subsequent investigation via Western blotting and immunofluorescence staining indicated that Bis-A induced formation but prevented degradation of autophagosomes. Mechanistic studies showed that Bis-A down-regulated phosphorylation of protein kinase B (AKT) and its downstream kinase, PRAS40, which is an mTOR repressor. Moreover, phosphorylation of p70S6K, an mTOR-dependent kinase, was also down-regulated. Down-regulation of these kinases suggests that the increase in LC3 lipidation may be due to mTOR deactivation. Thus, the cytostatic activity shown by Bis-A may be attributed to its induction of autophagosome formation. The Bis-A-induced autophagosome formation was suggested to be caused by its interference with the AKT-mTOR signaling pathway. |
| 巻・号 | 78(7) |
| ページ | 1656-62 |
| 公開日 | 2015-7-24 |
| DOI | 10.1021/acs.jnatprod.5b00258 |
| PMID | 26176165 |
| MeSH | Annexin A5 / metabolism Apoptosis / drug effects Apoptosis Regulatory Proteins / metabolism Autophagy Cell Line, Tumor Cytostatic Agents / chemistry Cytostatic Agents / pharmacology Down-Regulation Female Humans Indole Alkaloids / chemistry Indole Alkaloids / isolation & purification Indole Alkaloids / pharmacology* Malaysia Molecular Structure Phosphorylation Proto-Oncogene Proteins c-akt / metabolism TOR Serine-Threonine Kinases / drug effects Vinblastine / pharmacology |
| IF | 3.782 |
| 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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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 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 | A549 MCF7(RCB1904) |