Document Detail

Investigation of cell cycle arrest effects of actinomycin D at G1 phase using proteomic methods in B104-1-1 cells.
MedLine Citation:
PMID:  15964235     Owner:  NLM     Status:  MEDLINE    
Actinomycin D was previously reported as an inhibitor of Shc/Grb2 interaction in B104-1-1 cells. Actinomycin D arrested the cell cycle at the G1 phase at 1nM, which is about 10 times lower than the inhibition of Shc/Grb2 interactions in B104-1-1 cells. To evaluate other mechanisms of actinomycin D affected suppression of tumors and cell growth, except inhibition of Shc/Grb2 interactions, we examined the proteomic expression profile by proteomic technology. We found up-regulation of MEKK3 and down-regulation of Hsp70 expression from proteomic analysis, which is a very interesting observation because MEKK3 is strongly related with G1 arrest of cell cycle and Hsp70 is also involved in cell cycle regulation. These results indicate that the anti-tumor effects of actinomycin D is due to synergic effects of various proteins regulated by the compound including inhibition of the Shc/Grb2 interaction and other signaling pathways in the cytoplasm. Here we provide a mechanism-based explanation for growth inhibition by actinomycin D using proteomic technology. Thus, this approach may be a potentially useful method to reveal new mechanisms of active compounds or drugs with unknown cellular function.
Hyae-Kyeong Kim; Mi-Young Kong; Moon-Jin Jeong; Dong-Cho Han; Jung-Do Choi; Hak-Yong Kim; Kab-Seok Yoon; Jung-Min Kim; Kwang-Hee Son; Byoung-Mog Kwon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  37     ISSN:  1357-2725     ISO Abbreviation:  Int. J. Biochem. Cell Biol.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-07-12     Completed Date:  2005-10-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1921-9     Citation Subset:  IM    
Korea Research Institute of Bioscience and Biotechnology, Taejon.
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MeSH Terms
Biological Markers / metabolism*
Cells, Cultured
Dactinomycin / pharmacology*
G1 Phase / drug effects*
NIH 3T3 Cells
Receptor, erbB-2 / genetics,  metabolism
Signal Transduction*
Reg. No./Substance:
0/Biological Markers; 50-76-0/Dactinomycin; EC, erbB-2

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