Document Detail


Apoptosis-inducing active components from Corbicula fluminea through activation of caspase-2 and production of reactive oxygen species in human leukemia HL-60 cells.
MedLine Citation:
PMID:  16545898     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The anti-cancer effects and possible mechanisms of the freshwater clam (Corbicula fluminea Muller) and its active compounds (FME) on cell viability in human leukemia HL-60 cells were investigated. This study demonstrated that FME was able to inhibit cell proliferation in a concentration- and time-dependent manner. Treatment with FME caused induction of caspase-2, caspase-3, caspase-6, caspase-8, and caspase-9 activity in a time-dependent manner, but not affect caspase-1 activity; it induced the proteolysis of DNA fragmentation factor (DFF-45) and poly(ADP-ribose) polymerase (PARP). Induction of cell death by FME was completely prevented by a pan-caspase inhibitor, Z-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK) and a caspase-2 inhibitor, Z-Val-Asp-Val-Ala-Asp-FMK (Z-VDVAD-FMK). Furthermore, treatment with FME caused a rapid loss of mitochondrial transmembrane potential, stimulation of generation of reactive oxygen species (ROS), release of mitochondrial cytochrome c into cytosol, and GSH depletion. Anti-oxidants such as N-acetylcysteine, catalase, superoxide dismutase, allopurinol, and pyrrolidine dithiocarbamate, but not diphenylene iodonium, significantly inhibited FME-induced cell death. In addition, the results showed that FME-induced apoptosis was accompanied by up-regulation of Bax and Bad, and down-regulation of Bcl-2 and Bcl-XL. Taken together, induction of apoptosis on HL-60 cells by FME was mainly associated with ROS production, GSH depletion, mitochondrial dysfunction, and caspase activation.
Authors:
Ying-Tang Huang; Yi-Hsuan Huang; Tzhy-Chyuan Hour; Bonnie Sun Pan; Yeuk-Chuen Liu; Min-Hsiung Pan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-20
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  44     ISSN:  0278-6915     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-06-23     Completed Date:  2006-09-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1261-72     Citation Subset:  IM    
Affiliation:
Department of Marine Biotechnology, National Kaohsiung Marine University, Kaohsiung, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Chloromethyl Ketones / pharmacology
Animals
Antioxidants / pharmacology
Apoptosis / drug effects*
Caspase 2
Caspases / antagonists & inhibitors,  metabolism*
Cell Growth Processes / drug effects
Cell Survival / drug effects
Corbicula / chemistry*
Cytochromes c / secretion
Drug Interactions
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Flow Cytometry
Glutathione / metabolism
HL-60 Cells
Humans
Isoenzymes
Membrane Potentials / drug effects
Mitochondrial Membranes / drug effects,  physiology
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
Reactive Oxygen Species / antagonists & inhibitors,  metabolism*
Chemical
Reg. No./Substance:
0/Amino Acid Chloromethyl Ketones; 0/Antioxidants; 0/Enzyme Inhibitors; 0/Isoenzymes; 0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Oxygen Species; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 70-18-8/Glutathione; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 2; EC 3.4.22.-/Caspases

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