Document Detail


Gypenosides induced G0/G1 arrest via CHk2 and apoptosis through endoplasmic reticulum stress and mitochondria-dependent pathways in human tongue cancer SCC-4 cells.
MedLine Citation:
PMID:  18674953     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gypenosides (Gyp), a component of Gynostemma pentaphyllum Makino, was selected for examining the effects on the cell viability, cell cycle and induction of apoptosis in human tongue cancer SCC-4 cells. Gyp induced cytotoxicity (decreased the percentage of viable cells) in SCC-4 cells appeared to be associated with induction of cell cycle arrest (G0/G1 arrest), apoptotic cell death based on Gyp induced morphological changes and DNA fragmentation and increased the sub-G1 group in examined SCC-4 cells. The production of reactive oxygen species and Ca(2+) and the depolarization of mitochondrial membrane potential were observed, dose- and time-dependently, after treatment of SCC-4 cells with various concentrations of Gyp. Gyp inhibited the levels of the anti-apoptotic proteins Bcl-2 and Bcl-xl, but promoted the levels of the pro-apoptotic protein Bax. Western blotting showed the releases of cytochrome c and Endo G and both were also confirmed by confocal laser microscopic systems. The GADD153 moved to nuclei (nuclear translocation). In conclusion, Gyp induced ER stress and production of reactive oxygen species and Ca(2+), change the ratio of Bcl-2 and Bax, followed by the dysfunction of mitochondria, caused cytochrome c release, activation of caspase-3 before leading to apoptosis. These results provide information towards an understanding of the mechanisms by which Gyp induces cell cycle arrest and apoptosis in human tongue cancer cells.
Authors:
Jung-Chou Chen; Kung-Wen Lu; Ming-Li Tsai; Shu-Chun Hsu; Chao-Lin Kuo; Jai-Sing Yang; Te-Chun Hsia; Chun-Shu Yu; Su-Tze Chou; Ming-Ching Kao; Jing-Gung Chung; W Gibson Wood
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-31
Journal Detail:
Title:  Oral oncology     Volume:  45     ISSN:  1879-0593     ISO Abbreviation:  Oral Oncol.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-23     Completed Date:  2010-02-09     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  9709118     Medline TA:  Oral Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  273-83     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Carcinoma, Squamous Cell / pathology*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Endoplasmic Reticulum / pathology
G0 Phase / drug effects
G1 Phase / drug effects
Gynostemma
Humans
Mitochondria / pathology
Plant Extracts / pharmacology*
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
Reactive Oxygen Species / metabolism
Tongue Neoplasms / pathology*
bcl-2-Associated X Protein / biosynthesis
bcl-X Protein / antagonists & inhibitors
Chemical
Reg. No./Substance:
0/Plant Extracts; 0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Oxygen Species; 0/bcl-2-Associated X Protein; 0/bcl-X Protein; 0/gypenoside

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