Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-6-11
pubmed:abstractText
Mutation of Bcr-Abl is an important mechanism by which chronic myelogenous leukemia (CML) cells become resistant to Gleevec. The T315I mutation is clinically significant since CML cells harboring this mutation are insensitive to Gleevec and other Bcr-Abl-targeted drugs. Identification of new agents capable of effectively killing CML cells with T315I mutation would have important therapeutic implications in Gleevec-resistant CML. Here, we showed that beta-phenylethyl isothiocyanate (PEITC), a natural compound found in vegetables, is effective in killing CML cells expressing T315I BCR-ABL. Treatment of leukemia cell lines harboring wild-type or mutant Bcr-Abl with 10 microM PEITC resulted in an elevated ROS stress and a redox-mediated degradation of the BCR-ABL protein, leading to massive death of the leukemia cells. Antioxidant NAC attenuated the PEITC-induced oxidative stress in CML cells and prevented the degradation of BCR-ABL, caspase-3 activation and cell death. We further showed that the ROS-induced degradation of BCR-ABL was mediated partially by caspase-3 and the proteasome pathway. The ability of PEITC to effectively kill T315I-positive CML cells was further confirmed using primary leukemia cells isolated from CML patients. Our results suggest that PEITC is a promising compound capable of killing Gleevec-resistant CML cells through a ROS-mediated mechanism and warrants further investigations.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-10403855, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-10833515, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-11287972, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-11369642, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-11401302, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-11423618, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-11752224, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-11870241, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-12028026, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-12204532, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-12414617, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-12531810, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-12623848, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-12665579, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-14657961, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-15194504, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-15256671, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-15276073, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-15486067, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-15719031, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-15819723, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-16054126, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-16193082, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-16527898, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-16547503, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-16772610, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-16775234, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-16775240, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-16818614, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-16959615, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-17185463, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-17308109, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-17522713, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-17550858, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-17853901, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-8339266, http://linkedlifedata.com/resource/pubmed/commentcorrection/18385754-8408645
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Aldehyde Dehydrogenase, http://linkedlifedata.com/resource/pubmed/chemical/Anticarcinogenic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3, http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione, http://linkedlifedata.com/resource/pubmed/chemical/Isothiocyanates, http://linkedlifedata.com/resource/pubmed/chemical/Piperazines, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines, http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species, http://linkedlifedata.com/resource/pubmed/chemical/imatinib, http://linkedlifedata.com/resource/pubmed/chemical/phenethyl isothiocyanate
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-5551
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1191-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
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