Linked Life Data

10942236

Source:http://linkedlifedata.com/resource/pubmed/id/10942236

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2000-8-24
pubmed:abstractText
Fludarabine is a nucleotide analog effective in the clinical treatment of chronic lymphocytic leukemia (CLL) and other indolent lymphocytic malignancies. Although the incorporation of fludarabine into DNA is a key event in causing cytotoxicity in proliferating leukemia cells, the precise mechanisms by which fludarabine kills CLL cells remain unclear because of the quiescent nature of this malignancy. The present study demonstrated that inhibition of RNA transcription correlated significantly with the cytotoxic action of fludarabine in CLL cells. In contrast, suppression of the low level of DNA synthesis did not affect the survival of the leukemia cells. In addition, inhibition of fludarabine incorporation into cellular DNA through repair synthesis in CLL cells did not alter the cytotoxicity of this drug. Rather, inhibition of RNA synthesis by fludarabine led to a specific diminishment of certain cellular proteins from CLL cells. The combination of fludarabine with another RNA synthesis inhibitor, actinomycin D, or with the protein synthesis inhibitor, puromycin, substantially enhanced the cytotoxic activity against CLL cells. These results suggest that termination of mRNA transcription and the consequent depletion of proteins required for cell survival may be a novel biochemical mechanism of action of fludarabine in CLL cells. Thus, inhibition of RNA/protein synthesis may provide a new therapeutic strategy for the treatment of CLL patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1405-13
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Inhibition of RNA transcription: a biochemical mechanism of action against chronic lymphocytic leukemia cells by fludarabine.
pubmed:affiliation
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't