Linked Life Data

16273216

Source:http://linkedlifedata.com/resource/pubmed/id/16273216

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-11-7
pubmed:abstractText
Multidrug resistance (MDR) in tumor cells is generally associated with increased efflux of the cytotoxic compounds, due to the activation of mechanisms of intracellular transport and to the overexpression of surface proteins, such as P-glycoprotein (Pgp), which act as ATP-dependent molecular pumps. In a previous study, voacamine, a bisindolic alkaloid from Peschiera fuchsiaefolia, was examined for its possible capability of enhancing the cytotoxic effect of doxorubicin (DOX) on resistant human osteosarcoma cells. The effects of voacamine on the cell survival and on accumulation of DOX were investigated on both the parental cell line, U-2 OS-WT, and its resistant counterpart, U-2 OS-R. A differential effect between sensitive and resistant cells on the intracellular DOX concentration and distribution was revealed. In particular, voacamine induced a significant increase of drug retention and intranuclear location in resistant cells. Moreover, the cell survival analysis and the electron microscopic observations revealed an enhancement of the cytotoxic effect of DOX induced by the plant extract. In the present study, a panel of monoclonal antibodies (MAbs), recognizing different and specific structural and functional state of Pgp, was used. By flow cytometry and immunofluorescence confocal microscopy, a dose-dependent increase of the reactivity of Pgp with MAb UIC2, which specifically recognizes an epitope of the drug transporter in its functional conformation, was detected in voacamine-treated U-2 OS-R cells. Conversely, the expression of the epitope recognized by MAb MC57 was downregulated while MAb MM4.17 did not change its binding level to treated and untreated MDR cells. These data suggest that the plant extract reacts with Pgp producing conformational changes with consequent epitope modulation. Taken together, our observations seem to demonstrate that voacamine is a substrate for Pgp and, therefore, interferes with the Pgp-mediated drug export, acting as a competitive antagonist of cytotoxic agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1597-603
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16273216-Alkaloids, pubmed-meshheading:16273216-Antibodies, Monoclonal, pubmed-meshheading:16273216-Cell Line, Tumor, pubmed-meshheading:16273216-Cell Survival, pubmed-meshheading:16273216-Cyclosporine, pubmed-meshheading:16273216-Dose-Response Relationship, Drug, pubmed-meshheading:16273216-Doxorubicin, pubmed-meshheading:16273216-Drug Resistance, Multiple, pubmed-meshheading:16273216-Drug Resistance, Neoplasm, pubmed-meshheading:16273216-Flow Cytometry, pubmed-meshheading:16273216-Humans, pubmed-meshheading:16273216-Ibogaine, pubmed-meshheading:16273216-Microscopy, Confocal, pubmed-meshheading:16273216-Microscopy, Electron, Scanning, pubmed-meshheading:16273216-Osteosarcoma, pubmed-meshheading:16273216-P-Glycoproteins, pubmed-meshheading:16273216-Plant Bark, pubmed-meshheading:16273216-Plant Extracts
pubmed:year
2005
pubmed:articleTitle
Voacamine, an alkaloid extracted from Peschiera fuchsiaefolia, inhibits P-glycoprotein action in multidrug-resistant tumor cells.
pubmed:affiliation
Department of Technology and Health, Italian National Institute of Health, I-00161 Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't