Linked Life Data

11943391

Source:http://linkedlifedata.com/resource/pubmed/id/11943391

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2002-4-10
pubmed:abstractText
Internalization and subcellular fate of free doxorubicin or its polymeric conjugates based on poly N-(2-hydroxypropyl)methacrylamide (pHPMA), either non-targeted or targeted with anti-Thy1.2 or anti-CD71 monoclonal antibody was tested on EL-4 mouse T-cell lymphoma, SW620 human colorectal carcinoma and OVCAR-3 human ovarian adenocarcinoma. Doxorubicin fluorescence allowed us to follow the internalization and intracellular distribution of tested conjugates by laser scanning confocal microscopy and/or by fluorescent microscopy. Whereas free doxorubicin was always detectable only in the nuclei of treated cells, detectable fluorescence of doxorubicin bound to a polymeric carrier, targeted or non-targeted, was detectable up to 3 days of incubation only in the cytoplasmatic structures. While free doxorubicin causes apoptosis in the populations of tested cancer cell lines, significant number of apoptotic cells was never found in cell cultures exposed to targeted or non-targeted polymeric conjugates. In contrast to free doxorubicin, which is a strong inducer of p53 expression, increased p53 expression was never observed after the treatment with the polymeric drug. High-performance liquid chromatographic analysis shows that the percentage of cleaved doxorubicin is very low even after 48 h of incubation of tested cells with the polymeric conjugate, and cannot be the only reason for the toxicity of the conjugate. We suggest that: (a) after the treatment with pHPMA-bound drug, the cells die by necrosis and (b) the toxicity of pHPMA-based conjugates is a combination of the toxic effect of released doxorubicin and the toxic effect of doxorubicin in polymer-bound form directed against cell membranes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0168-3659
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
101-17
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Differences in the intracellular fate of free and polymer-bound doxorubicin.
pubmed:affiliation
Institute of Microbiology, Academy of Sciences of the Czech Republic, Department of Immunology and Gnotobiology, Vídenská 1083, Prague 4, 142 20, Czech Republic.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't