Title : Topotecan is a substrate for multidrug resistance associated protein 4.

Pub. Date : 2006 Jan

PMID : 16454695






17 Functional Relationships(s)
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Protein Name
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1 Topotecan is a substrate for multidrug resistance associated protein 4. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
2 This study aimed to investigate whether overexpression of human MRP4 rendered resistance to TPT by examining the cytotoxicity profiles using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) assay and cellular accumulation of TPT in HepG2 cells stably overexpressing MRP4. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
3 This study aimed to investigate whether overexpression of human MRP4 rendered resistance to TPT by examining the cytotoxicity profiles using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) assay and cellular accumulation of TPT in HepG2 cells stably overexpressing MRP4. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
4 The intracellular accumulation of TPT and paclitaxel (a PgP substrate) by V/HepG2 and MRP4/HepG2 cells was determined by incubation of TPT with the cells and the amounts of the drug in cells were determined by validated HPLC methods. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
5 The study demonstrated that MRP4 conferred a 12.03- and 6.86-fold resistance to TPT in the 4- and 48-hr drug-exposure MTT assay, respectively. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
6 BSO, MK-571, celecoxib, or diclofenac sensitised MRP4/HepG2 cells to TPT cytotoxicity and partially reversed MRP4-mediated resistance to TPT. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
7 BSO, MK-571, celecoxib, or diclofenac sensitised MRP4/HepG2 cells to TPT cytotoxicity and partially reversed MRP4-mediated resistance to TPT. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
8 In addition, the accumulation of TPT was significantly reduced in MRP4/HepG2 cells compared to V/HepG2 cells, and one-binding site model was found the best fit for the MRP4-mediated efflux of TPT, with an estimated K(m) of 1.66 microM and V(max) of 0.341 ng/min/106 cells. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
9 In addition, the accumulation of TPT was significantly reduced in MRP4/HepG2 cells compared to V/HepG2 cells, and one-binding site model was found the best fit for the MRP4-mediated efflux of TPT, with an estimated K(m) of 1.66 microM and V(max) of 0.341 ng/min/106 cells. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
10 In addition, the accumulation of TPT was significantly reduced in MRP4/HepG2 cells compared to V/HepG2 cells, and one-binding site model was found the best fit for the MRP4-mediated efflux of TPT, with an estimated K(m) of 1.66 microM and V(max) of 0.341 ng/min/106 cells. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
11 In addition, the accumulation of TPT was significantly reduced in MRP4/HepG2 cells compared to V/HepG2 cells, and one-binding site model was found the best fit for the MRP4-mediated efflux of TPT, with an estimated K(m) of 1.66 microM and V(max) of 0.341 ng/min/106 cells. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
12 Preincubation of MRP4/HepG2 cells with BSO (200 microM) for 24 hr, celecoxib (50 microM), or MK-571 (100 microM) for 2 hr significantly increased the accumulation of TPT over 10 min in MRP4/HepG2 cells by 28.0%, 37.3% and 32.5% (P < 0.05), respectively. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
13 Preincubation of MRP4/HepG2 cells with BSO (200 microM) for 24 hr, celecoxib (50 microM), or MK-571 (100 microM) for 2 hr significantly increased the accumulation of TPT over 10 min in MRP4/HepG2 cells by 28.0%, 37.3% and 32.5% (P < 0.05), respectively. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
14 These findings indicate that MRP4 confers resistance to TPT and TPT is the substrate for MRP4. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
15 These findings indicate that MRP4 confers resistance to TPT and TPT is the substrate for MRP4. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
16 These findings indicate that MRP4 confers resistance to TPT and TPT is the substrate for MRP4. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens
17 Further studies are needed to explore the role of MRP4 in resistance to, toxicity and pharmacokinetics of TPT in cancer patients. Topotecan ATP binding cassette subfamily C member 4 Homo sapiens