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Induction of incomplete autophagic response by cancer preventive geranylgeranoic acid in human hepatoma-derived cell line.
MedLine Citation:
PMID:  21787360     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Geranylgeranoic acid (GGA) is a natural polyprenoic acid derivatives of which have been shown to prevent second primary hepatoma. GGA induces mitochondriamediated programmed cell death (PCD), which may be relevant to cancer prevention. To gain further insights into GGA-induced PCD, autophagy processes were examined in human hepatoma-derived HuH-7 cells. Treatment of HuH-7/GFP-LC3 cells with GGA induced green fluorescent puncta in the cytoplasm within 30 min and their massive accumulation at 24 h. After 15 min of GGA treatment, a burst of mitochondrial superoxide production occurred and LC3β-I was appreciably converted to LC3β-II. GGA-induced early stages of autophagy were unequivocally confirmed by electron-microscopic observation of early/initial autophagic vacuoles. On the other hand, LC3β-II as well as p62/SQSTM1 continuously accumulated and colocalized in the cytoplasmic puncta after GGA treatment. Furthermore, GGA treatment of HuH- 7/mRFP-GFP-LC3 cells showed yellow fluorescent puncta, whereas glucose deprivation of the cells gave red fluorescent puncta. These results strongly suggest that GGA induces initial phase of autophagy, but blocks maturation process of autolysosomes or late stages of autophagy, insomuch that GGA provides substantial accumulation of autophagosomes under serum starvation condition in human hepatoma cells.
Authors:
Kyoko Okamoto; Yoko Sakimoto; Katsuyuki Imai; Haruki Senoo; Yoshihiro Shidoji
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-26
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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