|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0012780,
umls-concept:C0162638,
umls-concept:C0205263,
umls-concept:C0205409,
umls-concept:C0332281,
umls-concept:C0446228,
umls-concept:C0596952,
umls-concept:C0968798,
umls-concept:C1432694,
umls-concept:C1879547
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2003-10-21
|
|
pubmed:abstractText |
Myriadenolide is a diterpene that we have recently isolated from the extract of Alomia myriadenia (Asteraceae). Here we show for the first time that myriadenolide has caspase-dependent cytotoxic activity against human leukemia cells from both lymphocytic (Jurkat) and monocytic (THP-1) lineages, because preincubation of Jurkat or THP-1 cells with the broad-spectrum caspase inhibitor z-VAD-fmk completely abrogated cell death. Moreover, the mitochondrial pathway is implicated as mitochondrial depolarization and caspase-9 and caspase-3 activation were observed. Interestingly, caspase-8 and cleavage of the proapoptotic member of the Bcl-2 family BID was also observed during apoptosis induced by myriadenolide, suggesting a role for the caspase-8/BID pathway. However, interference with Fas or TNFR1 signaling did not interfere with apoptosis in our experimental system. Furthermore, pretreatment of cells with the caspase-3 inhibitor DEVD-fmk completely blocked the activation of caspase-8, suggesting that the activation of the caspase-8/BID pathway is part of an amplification loop initiated by caspase-3. Taken together, our results indicate myriadenolide as a novel candidate for the treatment of hematological malignancies.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/Diterpenes,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
0014-4827
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
290
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
420-6
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:14567999-Antigens, CD,
pubmed-meshheading:14567999-Antigens, CD95,
pubmed-meshheading:14567999-Apoptosis,
pubmed-meshheading:14567999-Asteraceae,
pubmed-meshheading:14567999-Blotting, Western,
pubmed-meshheading:14567999-Caspase 3,
pubmed-meshheading:14567999-Caspase 8,
pubmed-meshheading:14567999-Caspase 9,
pubmed-meshheading:14567999-Caspases,
pubmed-meshheading:14567999-Cell Cycle,
pubmed-meshheading:14567999-Cytochromes c,
pubmed-meshheading:14567999-Diterpenes,
pubmed-meshheading:14567999-Dose-Response Relationship, Drug,
pubmed-meshheading:14567999-Enzyme Activation,
pubmed-meshheading:14567999-Enzyme Inhibitors,
pubmed-meshheading:14567999-Humans,
pubmed-meshheading:14567999-Jurkat Cells,
pubmed-meshheading:14567999-Membrane Potentials,
pubmed-meshheading:14567999-Mitochondria,
pubmed-meshheading:14567999-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:14567999-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:14567999-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:14567999-Signal Transduction
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
Myriadenolide, a labdane diterpene isolated from Alomia myriadenia (asteraceae) induces depolarization of mitochondrial membranes and apoptosis associated with activation of caspases-8, -9, and -3 in Jurkat and THP-1 cells.
|
|
pubmed:affiliation |
Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, MG, Brazil.
|
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|
