ABCC1 p.Val20Cys
| Predicted by SNAP2: | A: N (72%), C: N (72%), D: N (53%), E: N (78%), F: N (82%), G: N (61%), H: N (66%), I: N (87%), K: N (61%), L: N (97%), M: N (87%), N: N (72%), P: N (72%), Q: N (87%), R: N (72%), S: N (78%), T: N (82%), W: N (66%), Y: N (82%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, W: N, Y: N, |
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[hide] Isolation of a multidrug resistance inhibitor from... Arch Pharm Res. 1998 Jun;21(3):344-7. Kim DK, Kwon HY, Lee KR, Rhee DK, Zee OP
Isolation of a multidrug resistance inhibitor from Aconitum pseudo-laeve var. erectum.
Arch Pharm Res. 1998 Jun;21(3):344-7., [PMID:9875455]
Abstract [show]
To overcome multidrug resistance (MDR) in cancer chemotherapy, we prepared various plant extracts and searched for a component which is effective for inhibition of MDR. MDR inhibition activity was determined by measuring cytotoxicity to MDR cells using multidrug resistant human fibrocarcinoma KB V20C, which is resistant to 20 nM vincristine and expresses high level of mdr1 gene. Of various plant extracts, the MeOH extract of the root of Aconitum pseudo-laeve var. erectum was found to have potent inhibitory activity on MDR. The bioassay-guided fractionation of the MeOH extract of the plant led to the isolation of an alkaloid, lycaconitine, as an active principle. And the IC50 of lycaconitine for KB V20C cells was 74 micrograms/ml.
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No. Sentence Comment
28 VCR- resistant KB V20C cells (generous gift of Dr. Cheng at Yale University, School of Medicine) were developed from the parental KB cells by stepwise selection for resistance with increasing concentration of VCR and cultured in the presence of 20 nM concentration of VCR.
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ABCC1 p.Val20Cys 9875455:28:18
status: NEW31 Cytotoxicity assay The KB V20C cells were maintained in drug free media 3 days before determination of the concentration capable of inhibiting 50% growth.
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ABCC1 p.Val20Cys 9875455:31:26
status: NEW37 And each fraction was examined for the anti-MDR activity in vitro, and the n-BuOH soluble fraction was found to have anti-MDR activity against KB V20C cells.
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ABCC1 p.Val20Cys 9875455:37:146
status: NEW43 erectum to cancer cells1~ 1 mg/ml IO0 llg/ml I0 llg/ml KB KB KB KB V20C KB7D KB V20C KB7D KB V20C KB7D 1 41.1 16.4 28.6 99.5 56.6 89.9 96.2 95.3 94.2 II 8.3 22.0 9.6 94.2 50.2 85.5 95.3 92 97.4 III 22.7 26.1 6.6 96.9 88.9 93.8 97.4 106.8 100.1 IV 42.5 27.3 6.1 98.5 105.6 95.1 97.9 100.3 98.5 l~Cell viability representsthe concentration IJ.Mof a compound required for 50% inhibition of cell growth.
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ABCC1 p.Val20Cys 9875455:43:67
status: NEWX
ABCC1 p.Val20Cys 9875455:43:80
status: NEWX
ABCC1 p.Val20Cys 9875455:43:93
status: NEW51 The MeOH extract of the roots of Aconitum pseudo-laeve var. erectum NAKAI (Ranunculaceae) showed significant modulating activity of Pgp-MDR against KB V20C but not MRP-MDR.
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ABCC1 p.Val20Cys 9875455:51:151
status: NEW[hide] Decreased drug accumulation without increased drug... Biochem Pharmacol. 1998 Apr 15;55(8):1199-211. Gaj CL, Anyanwutaku I, Chang YH, Cheng YC
Decreased drug accumulation without increased drug efflux in a novel MRP-overexpressing multidrug-resistant cell line.
Biochem Pharmacol. 1998 Apr 15;55(8):1199-211., [PMID:9719474]
Abstract [show]
KB/7D cells represent a multidrug-resistant subclone of human nasopharyngeal carcinoma KB cells generated by continuous exposure to the topoisomerase II inhibitor VP-16 (etoposide). KB/7D cells also show cross-resistance to doxorubicin and vincristine. Phenotypic traits of the cell line include a 2-fold decrease in topoisomerase II levels and a decrease in the uptake of VP-16 without an increase in the rate of drug efflux or expression of P-glycoprotein, suggesting a novel mechanism associated with the uptake of anticancer drugs. This study demonstrated that the multidrug-resistance associated protein (MRP) is overexpressed in KB/7D cells, and that the loss of resistance in revertant cells correlates with the loss of MRP. The resistance to VP-16 and doxorubicin could be overcome, partially, and resistance to vincristine could be overcome completely, by the L-enantiomer of verapamil, but not by the D-enantiomer or by BIBW 22 (4-[N-(2-hydroxy-2-methyl-propyl)-ethanolamino]-2,7-bis[cis-2,6-++ +dimethylmorpholino)-6-phenylpteridin), an inhibitor of MDR-1. L-Verapamil was shown to be significantly more potent than D-verapamil in modulating the accumulation defect in KB/7D cells towards doxorubicin, as measured by flow cytometry and confocal microscopy, and towards VP-16, as measured by increases in protein-linked DNA strand breaks. This suggests that KB/7D cells are multidrug resistant due to decreases in topoisomerase II levels and the overexpression of MRP, that MRP leads to a decrease in drug accumulation, and that L-verapamil can modulate the MRP-associated accumulation defect and drug-resistance phenotype. This contrasts with previous studies that suggest that MRP causes multidrug resistance by exporting cytotoxic drugs out of the cell and that did not show modulation of MRP by verapamil.
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No. Sentence Comment
39 P-gp-expressing KB/V20C [4] cells and KB/MDR cells [25] also have been described previously.
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ABCC1 p.Val20Cys 9719474:39:19
status: NEWX
ABCC1 p.Val20Cys 9719474:39:123
status: NEW41 Drug-resistant cells were maintained in drug-containing medium (7 M of VP-16 for KB/7D cells, 20 nM of vincristine for KB/V20C cells, and 37 nM of doxorubicin for KB/MDR cells).
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ABCC1 p.Val20Cys 9719474:41:130
status: NEW124 A partial revertant cell line, KB/7Dpr , which showed approximately 40-fold resistance to VP-16 and 4-fold resistance to vincristine when compared with KB cells, and known P-gp-expressing cell lines, V20C and KB/MDR, were included in these studies.
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ABCC1 p.Val20Cys 9719474:124:0
status: NEWX
ABCC1 p.Val20Cys 9719474:124:200
status: NEW126 V20C cells also showed no significant MRP expression at the RNA level.
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ABCC1 p.Val20Cys 9719474:126:0
status: NEW129 The KB/7Dpr cells lost most of this overexpression, while KB/7Dr and V20C cells did not show any amplification of the MRP gene.
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ABCC1 p.Val20Cys 9719474:129:69
status: NEW172 In all blots, 1 ؍ KB, 2 ؍Ȃc; KB/7D, 3 ؍ KB/7Dr , 4 ؍ KB/7Dpr , 5 ؍ KB/V20C, and 6 ؍ KB/MDR cells.
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ABCC1 p.Val20Cys 9719474:172:67
status: NEWX
ABCC1 p.Val20Cys 9719474:172:177
status: NEW192 KB/7D and V20C cells accumulated fewer PLDBs FIG. 2.
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ABCC1 p.Val20Cys 9719474:192:10
status: NEW37 P-gp-expressing KB/V20C [4] cells and KB/MDR cells [25] also have been described previously.
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ABCC1 p.Val20Cys 9719474:37:19
status: NEW122 A partial revertant cell line, KB/7Dpr , which showed approximately 40-fold resistance to VP-16 and 4-fold resistance to vincristine when compared with KB cells, and known P-gp-expressing cell lines, V20C and KB/MDR, were included in these studies.
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ABCC1 p.Val20Cys 9719474:122:200
status: NEW127 The KB/7Dpr cells lost most of this overexpression, while KB/7Dr and V20C cells did not show any amplification of the MRP gene.
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ABCC1 p.Val20Cys 9719474:127:69
status: NEW