ABCMdb

PMID: 26515463

Anreddy N, Patel A, Zhang YK, Wang YJ, Shukla S, Kathawala RJ, Kumar P, Gupta P, Ambudkar SV, Wurpel JN, Chen ZS, Guo H
A-803467, a tetrodotoxin-resistant sodium channel blocker, modulates ABCG2-mediated MDR in vitro and in vivo.
Oncotarget. 2015 Nov 17;6(36):39276-91. doi: 10.18632/oncotarget.5747., [PubMed]

Sentences

No. Mutations Sentence Comment

41 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly HEK293 cells transfected with wild-type (HEK293/R482) and mutant (HEK293/ R482G and HEK293/R482T) ABCG2 (Supplementary Figure S2) showed significant resistance to MX and topotecan compared to HEK293/pcDNA3.1 (Table 1). Login to comment 60 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly Table 1: A-803467 enhances the cytotoxicity of mitoxantrone and topotecan in HEK293/pcDNA3.1 cells overexpressing the wild-type as well as mutant ABCG2 Treatments IC50 &#b1; SD (nM) HEK293/ pcDNA3.1 FR HEK293/ R482 FR HEK293/ R482G FR HEK293/ R482T FR Mitoxantrone 24.8 &#b1; 0.9 1.0 258.5 &#b1; 12.8 10.4# 723.8 &#b1; 12.5 29.1# 808.0 &#b1; 38.2 32.4# +A-803467 (2.5 bc;M) 21.5 &#b1; 0.8 0.8 57.5 &#b1; 0.9 2.3* 66.2 &#b1; 1.2 2.6* 74.0 &#b1; 18.9 3.0* +A-803467 (7.5 bc;M) 20.4 &#b1; 2.0 0.9 19.5 &#b1; 0.2 0.8* 24.2 &#b1; 1.5 0.9* 34.5 &#b1; 16.7 1.3* +FTC (5 bc;M) 21.5 &#b1; 0.8 0.8 17.7 &#b1; 0.1 0.7* 22.4 &#b1; 1.2 0.9 36.5 &#b1; 18.7 1.4* Topotecan 10.2 &#b1; 2.5 1.0 280.9 &#b1; 30.6 27.5 224.2 &#b1; 12.6 22.0 187.2 &#b1; 19.6 18.4 +A-803467 (2.5 bc;M) 10.5 &#b1; 3.6 0.9 182.3 &#b1; 23.8 17.9 131.4 &#b1; 21.6 12.9 137.7 &#b1; 15.6 13.5 +A-803467 (7.5 bc;M) 9.4 &#b1; 3.7 0.9 18.6 &#b1; 4.6 1.8* 15.3 &#b1; 2.8 1.5* 17.4 &#b1; 3.8 1.7* +FTC (5 bc;M) 9.8 &#b1; 2.8 0.9 19.8 &#b1; 2.5 1.9* 16.4 &#b1; 2.4 1.6* 16.9 &#b1; 1.4 1.6* Cisplatin 2945.8 &#b1; 55.9 1.0 2636.0 &#b1; 94.1 0.9 2566.4 &#b1; 88.2 0.8 2745.6 &#b1; 141.8 0.9 +A-803467 (2.5 bc;M) 2486.7 &#b1; 90.1 0.8 2486.5 &#b1; 125.5 0.8 2478.8 &#b1; 70.6 0.8 2399.4 &#b1; 106.4 0.8 +A-803467 (7.5 bc;M) 2507.6 &#b1; 186.1 0.8 2377.7 &#b1; 125.3 0.8 2378.2 &#b1; 55.5 0.8 2377.7 &#b1; 125.3 0.8 +FTC (5 bc;M) 2641.4 &#b1; 84.2 0.8 2396.2 &#b1; 127.02 0.8 2367.5 &#b1; 27.6 0.9 2347.7 &#b1; 43.5 0.8 Data represents the mean IC50 values for each cell line &#b1; SD obtained from three independent sets of experiments. Login to comment 65 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly The fold resistance (FR) was determined by dividing the IC50 value of anticancer drug for HEK293/pcDNA3.1, HEK293/R482, HEK293/R482G and HEK293/R482T, in the absence or presence of reversal agents, by the IC50 value of respective anticancer drug for HEK293/pcDNA3.1 in the absence of reversal agent. FTC was used as a positive control of ABCG2 inhibitor Table 3: A-803467 cannot enhance the cytotoxicity of ABCB1 and ABCC10 substrate anticancer agents in HEK293/PCDNA3.1 cells overexpressing ABCB1 and ABCC10 Treatments IC50 &#b1; SD (nM) HEK293/pc DNA3.1 FR HEK293/ ABCB1 RF HEK293/ ABCC10 FR Paclitaxel 8.3 &#b1; 0.2 1.0 525.2 &#b1; 20.1 63.2# 95.2 &#b1; 6.1 11.4# +A-803467 (7.5 bc;M) 7.9 &#b1; 0.4 0.9 453 &#b1; 18.9 54.5 77.4 &#b1; 5.6 9.3 +Verapamil (5 bc;M) 8.2 &#b1; 0.6 1.0 9.5 &#b1; 1.5 1.0 * - - +Cepharanthine (2.5 bc;M) 7.2 &#b1; 0.3 0.8 - - 12.3 &#b1; 2.5 1.4* Data represents the mean IC50 values for each cell line &#b1; SD obtained from three independent sets of experiments. Login to comment 94 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly A. A-803467 at 7.5 bc;M significantly increased intracellular accumulation of [3 H]-MX in ABCG2-expressing cells HEK293/R482, HEK293/R482G and HEK293/R482T cells. Login to comment 164 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly Further functional analysis was performed by measuring the intracellular accumulation of [3 H]-MX in wild-type HEK293/R482, mutant HEK293/R482T, and mutant HEK293/R482G cells (Fig. 1A). Login to comment 238 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly Cell lines and cell culture HEK293/pcDNA3.1, wild-type HEK293/R482, mutant HEK293/R482T and mutant HEK293/R482G cells were established by transfecting HEK293 cell with either the empty pcDNA3.1 vector or pcDNA3.1 vector containing a full-length ABCG2, with coding arginine (R), threonine (T), or glycine (G) at amino acid position 482, respectively, after selection with G418 and maintained in medium with 2 mg/ml of G418 [26]. Login to comment 243 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly Cells were harvested and resuspended in a final concentration of 6 &#d7; 103 cells/well for HEK293/ pcDNA3.1, HEK/ABCB1, HEK/ABCC10, HEK293/R482, HEK293/R482G and HEK293/R482T cells, and 4 &#d7; 103 cells/well for H460 and H460/MX20 cells. Login to comment 295 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly Susan E. Bates and Robert W. Robey (NCI, NIH) for providing us HEK293/pcDNA3.1 (parental), HEK293/R482, HEK293/ R482G and HEK293/R482T, H460 and H460/MX20 cell lines. We thank Anna Maria Barbuti (St. John`s University, NY) for her critical reading and editing of the article. Login to comment