Table 1. IC50 values of the RAMBAs on cellular CYP26 and LNCaP cell growth inhibition assays.
|
Cell growth inhibitionb
|
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|---|---|---|---|---|
| Agents alone |
Combination with RAMBAsc
|
|||
| Compound | Cellular CYP26 assaya IC50 (nM) | IC50 (μM) | IC50 (μM) | Fold enhancement |
| ATRA | — | 4.3 | — | |
| VN/14-1 | 6.5±1.5 | 10.0 | 0.092* | +47 |
| VN/50-1 | 90.0±10.0 | 6.0 | 0.071* | +60 |
| VN/66-1 | 62.5±12.5 | 4.5 | 0.061* | +70 |
| VN/69-1 | 90.0±12.5 | 5.0 | 0.066* | +65 |
The cellular CYP26 assay was performed using [11,12-3H]-ATRA as a substrate for CYP26 with the addition of various concentrations of each RAMBA. The retinoids were extracted, processed, and analysed by HPLC. Percent metabolism vs the concentration of RAMBA used was obtained and graphed. IC50 values were determined as the concentration of RAMBA that inhibited the metabolism of [11,12-3H]-ATRA by 50%.
For cell growth inhibition studies, LNCaP cells were incubated with various concentrations of ATRA and the RAMBAs alone and in combination. The WST-1 assay was performed. The plot represents the percentage of viable cells vs the concentration of RAMBA used. The IC50 value was determined as the concentration of RAMBA that inhibited LNCaP cell viability by 50%.
1 μM of each RAMBA was used. Statistical significance was defined at the level of *P<0.05.