Table 1.
Comparison of drug efficacy on radioiodide uptake
| A | Drug | Mean value | TPC-1-NIS cells |
Human primary thyrocytes |
||||||
|---|---|---|---|---|---|---|---|---|---|---|
| na | Dose (μM)b | RAI uptakec | p valued | na | Dose (μM)b | RAI uptakec | p valued | |||
| 1 | carebastine | 3.45 | 3 | 1.0 | 3.8 ± 0.4 | 0.003 | 3 | 0.75 | 3.1 ± 0.6 | 0.040 |
| 2 | ebastine | 3.30 | 3 | 0.5 | 3.0 ± 0.5 | 0.020 | 3 | 0.25 | 3.6 ± 0.3 | 2.50 × 10−3 |
| 3 | chloroquinee | 3.00 | 3 | 50 | 2.6 ± 0.4 | 0.012 | 3 | 50 | 3.4 ± 0.1 | 9.00 × 10−4 |
| 4 | SAHA | 2.95 | 5 | 5 | 4.3 ± 0.2 | 5.50 × 10−7 | 6 | 5 | 1.6 ± 0.1 | 6.90 × 10−7 |
| 5 | astemizole | 2.80 | 3 | 0.25 | 3.5 ± 0.4 | 0.020 | 3 | 0.5–0.75 | 2.1 ± 0.1 | 7.00 × 10−4 |
| 6 | formoterol | 2.65 | 3 | 10 | 3.1 ± 0.2 | 0.001 | 3 | 1.0 | 2.2 ± 0.1 | 5.40 × 10−6 |
| 7 | clotrimazole | 2.60 | 3 | 0.25 | 3.3 ± 0.3 | 0.004 | 3 | 0.75 | 1.9 ± 0.2 | 0.019 |
| 8 | vatalanib | 2.50 | 4 | 1.0 | 1.6 ± 0.1 | 0.002 | 3 | 10 | 3.4 ± 0.3 | 0.002 |
| 9 | disulfiram | 2.35 | 5 | 0.5 | 2.2 ± 0.1 | 0.001 | 6 | 0.5 | 2.5 ± 0.1 | 8.90 × 10−6 |
| 10 | imatinib | 2.20 | 4 | 1.0 | 1.8 ± 0.2 | 0.020 | 3 | 1.0 | 2.6 ± 0.1 | 0.023 |
| 11 | fexofenadine | 2.05 | N/A | N/A | N/A | N/A | 3 | 2.0 | 4.1 ± 1.0 | 0.047 |
| 12 | niflumic acid | 1.75 | 4 | 15 | 1.7 ± 0.1 | 4.00 × 10−4 | 4 | 20 | 1.8 ± 0.1 | 2.40 × 10−5 |
| 13 | terfenadine | 1.75 | N/A | N/A | N/A | N/A | 3 | 1.0 | 3.5 ± 0.6 | 0.027 |
| 14 | pravastatin | 1.60 | 3 | 40 | 1.4 ± 0.1 | 0.003 | 3 | 40 | 1.8 ± 0.2 | 0.020 |
| 15 | phenformin | 1.60 | 3 | 250 | 1.9 ± 0.1 | 0.001 | 3 | 50 | 1.3 ± 0.1 | NS |
| 16 | zimelidine | 1.50 | 3 | 1.0 | 1.1 ± 0.01 | 0.003 | 3 | 1.0 | 1.9 ± 0.1 | 0.004 |
| B |
Drug combinations |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cell types | NFA |
SAHA |
DSF |
NFA |
DSF |
IMAT |
EBT |
CBT |
AST |
CLOT |
EBT |
CBT |
| CQ | CQ | CQ | SAHA | SAHA | SAHA | SAHA | SAHA | SAHA | SAHA | SEL | SEL | |
| Human thyrocytes | 7.3 | 4.3 | 3.5 | 2.4 | 1.1 | 1.5 | ||||||
| TPC-1-NIS | 0.9 | 8.3 | 1.8 | 2.2 | 3.3 | 3.0 | 6.3 | 5.2 | 7.9 | 6.8 | ||
| 8505C-NIS | 1.0 | 5.6 | 2.3 | 3.0 | 3.9 | 4.8 | ||||||
| Parental TPC-1 | 3.1 | 4.2 | 5.2 | 6.7 | 4.5 | 4.4 | ||||||
| Parental 8505C | 3.5 | 5.9 | 2.5 | 2.4 | ||||||||
| Parental MDA-MB-231 | 10.5 | 20.4 | 7.1 | 4.1 | ||||||||
| Mean value | 3.1 | 5.3 | 2.5 | 2.5 | 2.8 | 3.4 | 6.4 | 9.6 | 7.9 | 6.8 | 4.7 | 3.6 |
A, Drugs ranked on mean radioiodide uptake in TPC-1-NIS cells and human primary thyrocytes at maximal biological effect.
B, Mean radioiodide uptake in multiple cell types using drug combinations as indicated. Drugs included: niflumic acid (NFA), chloroquine (CQ), disulfiram (DSF), imatinib (IMAT), ebastine (EBT), carebastine (CBT), astemizole (AST), clotrimazole (CLOT), selumetinib (SEL), and suberoylanilide hydroxamic acid (SAHA).
N/A, not applicable; NS, not significant.
Number of biological replicates performed for each drug treatment. Each biological replicate typically consisted of three to four technical replicates.
Drug dose to achieve maximal radioiodide uptake. Astemizole data is compiled from treating human primary thyrocytes with two different doses (0.5 and 0.75 μM).
Mean fold increase in 125I uptake ± SEM for each drug relative to 0.1% DMSO as vehicle control, except for chloroquine (0.5% PBS), formoterol (0.2% DMSO), pravastatin (0.4% DMSO), and phenformin (0.25% ETOH).
p values determined using the unpaired two-tailed t test.
Cells treated for 24 h before assaying 125I uptake, except for chloroquine in which cells were treated for 8 h.