Source:http://linkedlifedata.com/resource/pubmed/id/19150344
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
|
pubmed:dateCreated |
2009-3-2
|
pubmed:abstractText |
Multidrug resistance protein 7 (MRP7; ABCC10) is an ABC transporter that confers resistance to anticancer agents such as the taxanes. We previously reported that several inhibitors of P-gp and MRP1 were able to inhibit the in vitro transport of E(2)17betaG by MRP7 in membrane vesicles transport assays. However, compounds that are able to reverse MRP7-mediated cellular resistance have not been identified. In this study, we examined the effects of cepharanthine (6',12'-dimethoxy-2,2'-dimethyl-6,7-[methylenebis(oxy)]oxyacanthan), an herbal extract isolated from Stephania cepharantha Hayata, to reverse paclitaxel resistance in MRP7-transfected HEK293 cells. Cepharanthine, at 2microM, completely reversed paclitaxel resistance in MRP7-transfected cells. In contrast, the effect of cepharanthine on the parental transfected cells was significantly less than that on the MRP7-transfected cells. In addition, cepharanthine significantly increased the accumulation of paclitaxel in MRP7-transfected cells almost to the level of control cells in the absence of cepharanthine. The efflux of paclitaxel from MRP7-transfected cells was also significantly inhibited by cepharanthine. The ability of cepharanthine to inhibit MRP7 was analyzed in membrane vesicle assays using E(2)17betaG, an established substrate of MRP7, as a probe. E(2)17betaG transport was competitively inhibited by cepharanthine with a K(i) value of 4.86microM. These findings indicate that cepharanthine reverses MRP7-mediated resistance to paclitaxel in a competitive manner.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABCC10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Benzylisoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Multidrug Resistance-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel,
http://linkedlifedata.com/resource/pubmed/chemical/cepharanthine
|
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
1873-2968
|
pubmed:author |
pubmed-author:AkiyamaShin-IchiS,
pubmed-author:AshbyCharles RCRJr,
pubmed-author:ChenXiangX,
pubmed-author:ChenZhe-ShengZS,
pubmed-author:DongChenC,
pubmed-author:FurukawaTatsuhikoT,
pubmed-author:Hopper-BorgeElizabethE,
pubmed-author:HuangXiao-CongXC,
pubmed-author:KruhGary DGD,
pubmed-author:KuangYe-HongYH,
pubmed-author:MeiR LRL,
pubmed-author:PengXing-XiangXX,
pubmed-author:ZhouYingY
|
pubmed:issnType |
Electronic
|
pubmed:day |
15
|
pubmed:volume |
77
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
993-1001
|
pubmed:dateRevised |
2009-5-21
|
pubmed:meshHeading |
pubmed-meshheading:19150344-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:19150344-Benzylisoquinolines,
pubmed-meshheading:19150344-Biological Transport, Active,
pubmed-meshheading:19150344-Cell Line,
pubmed-meshheading:19150344-Cell Line, Tumor,
pubmed-meshheading:19150344-Dose-Response Relationship, Drug,
pubmed-meshheading:19150344-Drug Resistance, Multiple,
pubmed-meshheading:19150344-Humans,
pubmed-meshheading:19150344-Multidrug Resistance-Associated Proteins,
pubmed-meshheading:19150344-Paclitaxel
|
pubmed:year |
2009
|
pubmed:articleTitle |
Cepharanthine is a potent reversal agent for MRP7(ABCC10)-mediated multidrug resistance.
|
pubmed:affiliation |
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY, USA.
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|