Linked Life Data

8097674

Source:http://linkedlifedata.com/resource/pubmed/id/8097674

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1993-6-1
pubmed:abstractText
Taxol is a naturally occurring chemotherapeutic agent that is active against a variety of tumors. Taxol is believed to act by binding tightly to microtubules and preventing their disaggregation. Others have shown that depletion of cellular glutathione results in the disaggregation of microtubules, presumably by allowing the oxidation of some or all of the cysteine residues in tubulins. We studied the effect of glutathione (GSH) depletion by L-buthionine sulfoximine (L-BSO) on taxol cytotoxicity in two human tumor lines. After a 24-h incubation in 5 mM L-BSO, the breast adenocarcinoma line MCF-7 and the lung adenocarcinoma line A549 were exposed to varying concentrations of taxol for 24 h. GSH levels were undetectable in cells treated with L-BSO. At the highest concentrations of taxol (50 nM), control MCF-7 cells had 10% cell survival and control A549 cells had only 1% cell survival as assessed by clonogenic assay. Pretreatment with 5 mM L-BSO resulted in a 3-fold increase in survival of MCF-7 cells and a 10-fold increase in survival of A549 cells. Pretreatment with L-BSO had no effect on taxol uptake into A549 or MCF-7 cells, as assessed by measurement of binding of [3H]taxol to cells. Following exposure to 37 nM taxol for 24 h, both cell lines had over 80% of their population in G2/M and bromodeoxyuridine labeling showed that taxol markedly reduced the percentage of cells in S phase. L-BSO pretreatment had no effect on the cell cycle in either cell line in the absence of taxol. However, in cells treated with taxol, L-BSO increased the percentage of cells in S phase by 3-fold in both cell lines. We conclude that depletion of cellular GSH by L-BSO results in resistance to taxol in MCF-7 and A549 cells. Resistance to taxol mediated by GSH depletion is not due to alterations in cellular uptake of taxol by L-BSO. L-BSO increased the S-phase fraction of taxol-treated cells in both cell lines. These data suggest that GSH depletion interferes with cell cycle changes induced by taxol. The alteration in taxol-induced cell cycle effects may account for the resistance to taxol produced by L-BSO.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2066-70
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Glutathione depletion by L-buthionine sulfoximine antagonizes taxol cytotoxicity.
pubmed:affiliation
Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article, In Vitro