Linked Life Data

9615782

Source:http://linkedlifedata.com/resource/pubmed/id/9615782

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2A
pubmed:dateCreated
1998-6-18
pubmed:abstractText
The accumulation of adriamycin (ADR), daunomycin (DAUNO) and their glutathione (GSH)-conjugates, recently obtained by anaerobic reaction of the parent anthracyclines with reduced GSH, was examined in drug-sensitive and multidrug resistant (MDR) cell lines using confocal laser scanning microscopy. In all drug-sensitive lines used (TVM-A12 and TVM-A197 human melanoma cells, K562 lymphoblastoid cells and MCF-7 human breast cancer cells) ADR and DAUNO were mostly located in the nuclei, while their GSH-conjugates were found only in the cytoplasm, predominantly in the Golgi region. On the contrary, in MDR MCF-7/Dox cells, both conjugated and non conjugated anthracyclines gave fluorescence only in the cytoplasm, mostly in the Golgi region, the intensity of the fluorescence being stronger in cells pretreated with verapamil. Viability assay showed that the GSH-conjugate are significantly less cytotoxic than the parent anthracyclines in sensitive cells and showed the same scarce cytotoxicity in MDR MCF-7/Dox cells. These results demonstrate that conjugation of anthracycline antitumor drugs with GSH prevents their access to the nucleus and decreases their cytotoxicity. Furthermore, the observations on MCF-7/Dox suggest that GSH-conjugation of anthracycline might occur in resistant cells and can be in part responsible for the MDR in breast cancer cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0250-7005
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1159-66
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
Cytoplasmic localization of anthracycline antitumor drugs conjugated with reduced glutathione: a possible correlation with multidrug resistance mechanisms.
pubmed:affiliation
Institute of Experimental Medicine, National Research Council, Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't