Document Detail

6-Shogaol, an active constituent of dietary ginger, induces autophagy by inhibiting the AKT/mTOR pathway in human non-small cell lung cancer A549 cells.
MedLine Citation:
PMID:  19799425     Owner:  NLM     Status:  MEDLINE    
This study is the first study to investigate the anticancer effect of 6-shogaol in human non-small cell lung cancer A549 cells. 6-Shogaol inhibited cell proliferation by inducing autophagic cell death, but not, predominantly, apoptosis. Pretreatment of cells with 3-methyladenine (3-MA), an autophagy inhibitor, suppressed 6-shogaol mediated antiproliferation activity, suggesting that induction of autophagy by 6-shogaol is conducive to cell death. We also found that 6-shogaol inhibited survival signaling through the AKT/mTOR signaling pathway by blocking the activation of AKT and downstream targets, including the mammalian target of rapamycin (mTOR), forkhead transcription factors (FKHR) and glycogen synthase kinase-3beta (GSK-3beta). Phosphorylation of both of mTOR's downstream targets, p70 ribosomal protein S6 kinase (p70S6 kinase) and 4E-BP1, was also diminished. Overexpression of AKT by AKT cDNA transfection decreased 6-shogaol mediated autophagic cell death, supporting inhibition of AKT beneficial to autophagy. Moreover, reduction of AKT expression by siRNA potentiated 6-shogaol's effect, also supporting inhibition of AKT beneficial to autophagy. Taken together, these findings suggest that 6-shogaol may be a promising chemopreventive agent against human non-small cell lung cancer.
Jen-Yu Hung; Ya-Ling Hsu; Chien-Te Li; Ying-Chin Ko; Wen-Chiu Ni; Ming-Shyan Huang; Po-Lin Kuo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of agricultural and food chemistry     Volume:  57     ISSN:  1520-5118     ISO Abbreviation:  J. Agric. Food Chem.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-10-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374755     Medline TA:  J Agric Food Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9809-16     Citation Subset:  IM    
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
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MeSH Terms
Apoptosis / drug effects
Autophagy / drug effects*
Carcinoma, Non-Small-Cell Lung / drug therapy,  genetics,  metabolism*,  physiopathology
Catechols / pharmacology*
Cell Line, Tumor
Ginger / chemistry*
Intracellular Signaling Peptides and Proteins / genetics,  metabolism*
Plant Extracts / pharmacology*
Protein-Serine-Threonine Kinases / genetics,  metabolism*
Proto-Oncogene Proteins c-akt / genetics,  metabolism*
Signal Transduction / drug effects*
Reg. No./Substance:
0/Catechols; 0/Intracellular Signaling Peptides and Proteins; 0/Plant Extracts; 555-66-8/shogaol; EC 2.7.1.-/mTOR protein; EC Kinases; EC Proteins c-akt

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