Source:http://linkedlifedata.com/resource/pubmed/id/15894295
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2005-6-7
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pubmed:abstractText |
The mechanisms involved in the apoptotic effect of LCY-2-CHO [9-(2-chlorobenzyl)-9H-carbazole-3-carbaldehyde], a synthetic carbazole derivative identified as an anti-inflammatory compound, were studied. Cell cycle analysis by propidium iodide staining in human THP-1 monocytic leukemia cells showed the ability of LCY-2-CHO to increase cell population in sub-G1 stage with time- and concentration-dependent manners. LCY-2-CHO-mediated cell death was also demonstrated by DNA laddering and was not related to the release of lactate dehydrogenase. Apoptosis in THP-1 cells induced by LCY-2-CHO was accompanied by the Bid cleavage, collapse of mitochondrial transmembrane potential, the release of cytochrome c and the activation of caspase-3. The apoptotic effect of LCY-2-CHO was diminished by the presence of zVEID-fmk (caspase-6 inhibitor), zIETD-fmk (caspase-8 inhibitor), and zVAD-fmk (non-selective caspase inhibitor), but was not altered by several antioxidants, and cathepsin inhibitor. The Bid cleavage and loss of mitochondrial transmembrane potential, but not the cytochrome c release, were reversed by zIETD-fmk. Comparing the cell selectivity of LCY-2-CHO, we found T-cell acute lymphoblastic CEM leukemia cells were sensitive to 1 microM LCY-2-CHO, acute myeloid leukemia HL-60 cells underwent apoptosis at 10 microM, while adherent cancer cells, such as PC3, HT29 and MCF-7, were resistant to 30 microM LCY-2-CHO within 24-h incubation. Taken together in the present study, we demonstrated LCY-2-CHO might be apoptotic for malignant hematopoietic cells but not anchorage-dependent cells. This action is mediated by an intrinsic caspase-dependent apoptotic event involving mitochondria.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/9-(2-chlorobenzyl)-9H-carbazole-3-ca...,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Carbazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
102-12
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15894295-Anti-Inflammatory Agents,
pubmed-meshheading:15894295-Apoptosis,
pubmed-meshheading:15894295-Carbazoles,
pubmed-meshheading:15894295-Caspases,
pubmed-meshheading:15894295-Cathepsins,
pubmed-meshheading:15894295-Cell Line, Tumor,
pubmed-meshheading:15894295-Cytochromes c,
pubmed-meshheading:15894295-DNA Fragmentation,
pubmed-meshheading:15894295-Enzyme Activation,
pubmed-meshheading:15894295-Humans,
pubmed-meshheading:15894295-Membrane Potentials,
pubmed-meshheading:15894295-Mitochondria,
pubmed-meshheading:15894295-Reactive Oxygen Species
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pubmed:year |
2005
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pubmed:articleTitle |
Cell apoptosis induced by a synthetic carbazole compound LCY-2-CHO is mediated through activation of caspase and mitochondrial pathways.
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pubmed:affiliation |
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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