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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-4-15
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pubmed:abstractText |
The triazine derivative 12459 is a potent G-quadruplex interacting agent that inhibits telomerase activity. This agent induces time- and dose-dependent telomere shortening, senescence-like growth arrest and apoptosis in the human A549 tumour cell line. We show here that 12459 induces a delayed apoptosis that activates the mitochondrial pathway. A549 cell lines selected for resistance to 12459 and previously characterized for an altered hTERT expression also showed Bcl-2 overexpression. Transfection of Bcl-2 into A549 cells induced a resistance to the short-term apoptotic effect triggered by 12459, suggesting that Bcl-2 is an important determinant for the activity of 12459. In sharp contrast, the Bcl-2 overexpression was not sufficient to confer resistance to the senescence-like growth arrest induced by prolonged treatment with 12459. We also show that 12459 provokes a rapid degradation of the telomeric G-overhang in conditions that paralleled the apoptosis induction. In contrast, the G-overhang degradation was not observed when apoptosis was induced by camptothecin. Bcl-2 overexpression did not modify the G-overhang degradation, suggesting that this event is an early process uncoupled from the final apoptotic pathway.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-10338214,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-10440377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-10472781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-10799836,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-11092831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-11572773,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-11641426,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-11842096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-11854467,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-11923537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-11961134,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-12120414,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-12398889,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-12409451,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-12467228,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-12515865,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-12646945,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-12760039,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-12782571,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-12810655,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-12917635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-14525974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-14559794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-14573759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-14729921,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-14760100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-15189140,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-15277522,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-15381071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-15486186,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-15703842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-15735037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-7568133,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-9054505,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15831792-9353250
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
1362-4962
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2192-203
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15831792-Antineoplastic Agents,
pubmed-meshheading:15831792-Apoptosis,
pubmed-meshheading:15831792-Cell Aging,
pubmed-meshheading:15831792-Cell Line, Tumor,
pubmed-meshheading:15831792-Drug Resistance, Neoplasm,
pubmed-meshheading:15831792-Guanine,
pubmed-meshheading:15831792-Humans,
pubmed-meshheading:15831792-Mitochondria,
pubmed-meshheading:15831792-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15831792-Quinolinium Compounds,
pubmed-meshheading:15831792-Telomere,
pubmed-meshheading:15831792-Triazines
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pubmed:year |
2005
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pubmed:articleTitle |
Overexpression of Bcl-2 is associated with apoptotic resistance to the G-quadruplex ligand 12459 but is not sufficient to confer resistance to long-term senescence.
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pubmed:affiliation |
Laboratoire d'Onco-Pharmacologie, JE 2428, UFR de Pharmacie, Université de Reims Champagne-Ardenne 51 rue Cognacq-Jay, 51096 Reims, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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