Induction of luciferase activity
| Compound . | γ/γ + β globin expression, range . | Mean-fold increase . | P . |
|---|---|---|---|
| Control, untreated | 0.015-0.022 | Baseline | N/A |
| AB | 0.029-0.047 | 1.8 | .01 |
| AMHCA | 0.028-0.038 | 2.0 | .01 |
| DMB | 0.033-0.052 | 2.2 | .01 |
| PAA | 0.021-0.033 | 1.4 | .01 |
| 3-(3,4 Dimethoxyphenyl)-propionic acid | 0.030-0.053 | 2.1 | .01 |
| 4-(3,4 Dimethoxyphenyl)-butyric acid | 0.035-0.053 | 1.9 | .01 |
| 2-Methylbutyric acid | 0.035-0.053 | 2.1 | .01 |
| 3,5 Dimethoxy-4-hydroxycinnamic acid | 0.029-0.048 | 1.9 | .01 |
| Cinnamic acid | 0.025-0.046 | 1.9 | .01 |
| Sodium butyryl hydroxamate | 0.032-0.051 | 1.7 | .01 |
| E-3-3 pyridyl-2 propanoic acid | 0.034-0.050 | 1.8 | .05 |
| Levulinic acid | 0.025-0.045 | 2.1 | .01 |
| Kemp triacid | 0.024-0.042 | 1.5 | .01 |
| Compound . | γ/γ + β globin expression, range . | Mean-fold increase . | P . |
|---|---|---|---|
| Control, untreated | 0.015-0.022 | Baseline | N/A |
| AB | 0.029-0.047 | 1.8 | .01 |
| AMHCA | 0.028-0.038 | 2.0 | .01 |
| DMB | 0.033-0.052 | 2.2 | .01 |
| PAA | 0.021-0.033 | 1.4 | .01 |
| 3-(3,4 Dimethoxyphenyl)-propionic acid | 0.030-0.053 | 2.1 | .01 |
| 4-(3,4 Dimethoxyphenyl)-butyric acid | 0.035-0.053 | 1.9 | .01 |
| 2-Methylbutyric acid | 0.035-0.053 | 2.1 | .01 |
| 3,5 Dimethoxy-4-hydroxycinnamic acid | 0.029-0.048 | 1.9 | .01 |
| Cinnamic acid | 0.025-0.046 | 1.9 | .01 |
| Sodium butyryl hydroxamate | 0.032-0.051 | 1.7 | .01 |
| E-3-3 pyridyl-2 propanoic acid | 0.034-0.050 | 1.8 | .05 |
| Levulinic acid | 0.025-0.045 | 2.1 | .01 |
| Kemp triacid | 0.024-0.042 | 1.5 | .01 |
Luciferase activity was driven by the γ globin gene promoter by 12 SCFADs or butyrate, from a construct containing the μLCR β globin gene promoter-Renilla luciferase + γ globin gene promoter-firefly luciferase. This construct shows preferential β globin gene expression at baseline. Mean induction of the firefly luciferase driven by the γ globin gene promoter ranged from 1.4- to 2-fold over untreated control cells in 3 to 5 assays and was similar to the activity of arginine butyrate, which resulted in 1.8-fold induction of the γ globin gene promoter. Compounds were active at 0.5 mM, except for phenoxyacetic acid, which was active at 2.0 mM. The increase in γ globin expression over control was statistically significant with these tested compounds.
N/A indicates not applicable.