2015年7月
Bisleuconothine A Induces Autophagosome Formation by Interfering with AKT-mTOR Signaling Pathway
JOURNAL OF NATURAL PRODUCTS
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- 巻
- 78
- 号
- 7
- 開始ページ
- 1656
- 終了ページ
- 1662
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1021/acs.jnatprod.5b00258
- 出版者・発行元
- AMER CHEMICAL SOC
We have previously reported that bisleuconothine A (Bis-A), a novel bisindole alkaloid isolated from Leuconotis griffithii, showed cytostatic activity in several tell 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 phosphotylation 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 Pis-A-induced autophagosome formation was suggested to be caused by its interference with the AKT-mTOR signaling pathway.
- リンク情報
- ID情報
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- DOI : 10.1021/acs.jnatprod.5b00258
- ISSN : 0163-3864
- eISSN : 1520-6025
- Web of Science ID : WOS:000358700000023