Document Detail


Apoptosis induction of human leukemia cells by Streptomyces sp. SY-103 metabolites through activation of caspase-3 and inactivation of Akt.
MedLine Citation:
PMID:  19956899     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
We isolated 23 marine actinomycetes from seawater samples. Of these, strain SY-103 exhibited the strongest cytotoxic activity on human leukemic cell lines. Biochemical tests and 16S rDNA sequencing of this strain allowed us to identify SY-103 as a strain of the genus Streptomyces. In the present study, the pure cytotoxic compound (PCC) from Streptomyces sp. SY-103 metabolites was purified by reverse-phase HPLC and the biochemical mechanisms of PCC-induced apoptosis in cultured human leukemic cell lines were investigated. The exposure of cells to PCC resulted in growth inhibition and induction of apoptosis, which was associated with the proteolytic activation of caspase-3 and down-regulation of anti-apoptotic Bcl-2 protein. However, PCC-induced caspase-3 activation and apoptosis were significantly attenuated in Bcl-2 overexpressing U937 cells. z-DEVD-fmk, a caspase-3 specific inhibitor, blocked caspase-3 activation and increased the survival rate of PCC-treated U937 cells. The activity of Akt was also inhibited in PCC-treated cells, and phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor, LY294002, sensitized the cells to PCC-induced apoptosis indicating that the down-regulation of the Akt signaling pathway plays a key role in PCC-induced apoptosis. Our findings imply that some of the biological functions of Bcl-2 and PI3K/Akt are attributed to their ability to inhibit PCC-induced apoptosis; therefore, it is suggested that this compound is a promising anti-cancer agent for leukemia cells.
Authors:
Seong-Yun Jeong; Min Ho Han; Cheng-Yun Jin; Gi-Young Kim; Byung Tae Choi; Taek-Jeong Nam; Se-Kwon Kim; Yung Hyun Choi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  25     ISSN:  1791-244X     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  31-40     Citation Subset:  IM    
Affiliation:
Department of Medical Life Science, Catholic University of Daegu, Daegu 712-702, Republic of Korea.
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