Source:http://linkedlifedata.com/resource/pubmed/id/17640301
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
2007-8-13
|
| pubmed:abstractText |
Through extensive screening of marine sponge compounds, the authors have found that sipholenol A, a sipholane triterpene isolated from the Red Sea sponge, Callyspongia siphonella, potently reversed multidrug resistance (MDR) in cancer cells that overexpressed P-glycoprotein (P-gp). In experiments, sipholenol A potentiated the cytotoxicity of several P-gp substrate anticancer drugs, including colchicine, vinblastine, and paclitaxel, but not the non-P-gp substrate cisplatin, and significantly reversed the MDR of cancer cells KB-C2 and KB-V1 in a concentration-dependent manner. Furthermore, sipholenol A had no effect on the response to cytotoxic agents in cells lacking P-gp expression or expressing MDR protein 1 or breast cancer resistance protein. Sipholenol A (IC(50) > 50 microM) is not toxic to all the cell lines that were used, regardless of their membrane transporter status. Accumulation and efflux studies with the P-gp substrate [(3)H]-paclitaxel demonstrated that sipholenol A time-dependently increased the intracellular accumulation of [(3)H]-paclitaxel by directly inhibiting P-gp-mediated drug efflux. In addition, sipholenol A did not alter the expression of P-gp after treating KB-C2 and KB-V1 cells for 36 h and 72 h. However, it efficaciously stimulated the activity of ATPase of P-gp and inhibited the photolabeling of this transporter with its transport substrate [(125)I]-iodoarylazidoprazosin. Overall, the present results indicate that sipholenol A efficiently inhibits the function of P-gp through direct interactions, and sipholane triterpenes are a new class of potential reversing agents for treatment of MDR in P-gp-overexpressing tumors.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABCB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ABCG2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Azides,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Multidrug Resistance-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Photoaffinity Labels,
http://linkedlifedata.com/resource/pubmed/chemical/Prazosin,
http://linkedlifedata.com/resource/pubmed/chemical/Triterpenes,
http://linkedlifedata.com/resource/pubmed/chemical/azidoprazosin,
http://linkedlifedata.com/resource/pubmed/chemical/multidrug resistance-associated...
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
1347-9032
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
98
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1373-80
|
| pubmed:meshHeading |
pubmed-meshheading:17640301-ATP-Binding Cassette Transporters,
pubmed-meshheading:17640301-Animals,
pubmed-meshheading:17640301-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:17640301-Azides,
pubmed-meshheading:17640301-Callyspongia,
pubmed-meshheading:17640301-Cell Line, Tumor,
pubmed-meshheading:17640301-Drug Resistance, Multiple,
pubmed-meshheading:17640301-Drug Resistance, Neoplasm,
pubmed-meshheading:17640301-Humans,
pubmed-meshheading:17640301-Iodine Radioisotopes,
pubmed-meshheading:17640301-KB Cells,
pubmed-meshheading:17640301-Multidrug Resistance-Associated Proteins,
pubmed-meshheading:17640301-Neoplasm Proteins,
pubmed-meshheading:17640301-P-Glycoprotein,
pubmed-meshheading:17640301-Photoaffinity Labels,
pubmed-meshheading:17640301-Prazosin,
pubmed-meshheading:17640301-Triterpenes
|
| pubmed:year |
2007
|
| pubmed:articleTitle |
Sipholenol A, a marine-derived sipholane triterpene, potently reverses P-glycoprotein (ABCB1)-mediated multidrug resistance in cancer cells.
|
| pubmed:affiliation |
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St John's University, Jamaica, NY 11439, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Intramural
|