論文

査読有り
2015年7月

Bisleuconothine A Induces Autophagosome Formation by Interfering with AKT-mTOR Signaling Pathway

JOURNAL OF NATURAL PRODUCTS
  • Chin Piow Wong
  • ,
  • Ari Seki
  • ,
  • Kaori Horiguchi
  • ,
  • Tomokazu Shoji
  • ,
  • Takashi Arai
  • ,
  • Alfarius Eko Nugroho
  • ,
  • Yusuke Hirasawa
  • ,
  • Fumiaki Sato
  • ,
  • Toshio Kaneda
  • ,
  • Hiroshi Morita

78
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
DOI
https://doi.org/10.1021/acs.jnatprod.5b00258
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000358700000023&DestApp=WOS_CPL
ID情報
  • DOI : 10.1021/acs.jnatprod.5b00258
  • ISSN : 0163-3864
  • eISSN : 1520-6025
  • Web of Science ID : WOS:000358700000023

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