Document Detail


Interaction of Ganoderma triterpenes with doxorubicin and proteomic characterization of the possible molecular targets of Ganoderma triterpenes.
MedLine Citation:
PMID:  18422750     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Triterpenes are the main components with cytotoxicity in Ganoderma lucidum, which is used popularly as a complementary treatment for cancer therapy in traditional Chinese medicine. To investigate the possible interaction between chemotherapeutic agents and triterpenes extracted from G. lucidum, the cytotoxicity of doxorubicin (DOX) combined with Ganoderma triterpenes (GTS) or lucidenic acid N (LCN), a purified compound, was examined in HeLa cells. The combinations targeting DOX with GTS or LCN resulted in a synergistic interaction in HeLa cells. Moreover, to identify the molecular targets of GTS, two-dimensional gel electrophoresis-based comparative proteomics was carried out and proteins with altered expression levels after GTS treatment in HeLa cells were identified by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. The results of our proteomic study indicated that the GTS treatment caused regulated expression of 14 proteins, which play important roles in cell proliferation, the cell cycle, apoptosis, and oxidative stress. Flow cytometric analysis confirmed that GTS could induce weak G(0)-G(1) phase arrest and combined use of GTS with DOX could induce apoptosis in cells. Furthermore, GTS enhanced the reactive oxygen species (ROS)-producing effect of DOX, and a ROS scavenger could affect the synergism between GTS and DOX. In cells with high Ku80 protein expression, the synergism between GTS and DOX was also partly affected. Importantly, in cells with high Ku80 expression that were treated with a ROS scavenger, the synergism between GTS and DOX totally disappeared. These results suggest that the synergism between GTS and DOX might be based on GTS-induced sensitization of cells to chemotherapeutics through enhanced oxidative stress, DNA damage, and apoptosis.
Authors:
Qing-Xi Yue; Fu-Bo Xie; Shu-Hong Guan; Chao Ma; Min Yang; Bao-Hong Jiang; Xuan Liu; De-An Guo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-16
Journal Detail:
Title:  Cancer science     Volume:  99     ISSN:  1349-7006     ISO Abbreviation:  Cancer Sci.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-05-30     Completed Date:  2008-06-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1461-70     Citation Subset:  IM    
Affiliation:
Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Nuclear / analysis
Blotting, Western
Cell Cycle / drug effects
DNA-Binding Proteins / analysis
Doxorubicin / pharmacology*
Drug Synergism
Ganoderma / chemistry*
Hela Cells
Humans
Neoplasm Proteins / analysis*
Protein Phosphatase 2 / physiology
Proteomics*
Reactive Oxygen Species / metabolism
Triterpenes / pharmacology*
Chemical
Reg. No./Substance:
0/Antigens, Nuclear; 0/DNA-Binding Proteins; 0/Ku autoantigen; 0/Neoplasm Proteins; 0/Reactive Oxygen Species; 0/Triterpenes; 0/lucidenic acid N; 23214-92-8/Doxorubicin; EC 3.1.3.16/PPP2CA protein, human; EC 3.1.3.16/Protein Phosphatase 2

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