Table 1.
LC90 and LC99 values for vorinostat, flavopiridol and their combination
| Cell Lines | LC90 (μM) | CI IC90* | LC99 (μM) | CI IC99 | ||||
|---|---|---|---|---|---|---|---|---|
| V | FL | V + FL | V | FL | V + FL | |||
| Wild-type TP53 | ||||||||
| SK-N-BE(1) | 1.8 | 0.2 | 0.7 + 0.1 | 1.0 ± 0.3 | >2.0 | 1.0 | >2.0 + >0.4 | ND |
| SK-N-RA | >2.0¶ | >0.4 | >2.0 + >0.4 | ND§ | >2.0 | >0.4 | >2.0 + >0.4 | ND |
| CHLA-79 | >2.0 | 0.4 | 1.4 + 0.3 | 0.8 ± 0.3 | >2.0 | 0.4 | 1.7 + 0.3 | 0.8 ± 0.4 |
| CHLA-136 | >2.0 | 0.4 | 1.3 + 0.3 | 0.7 ± 0.2 | >2.0 | >0.4 | >2.0 + >0.4 | 0.5 ± 0.3 |
| Mutant TP53 | ||||||||
| SK-N-BE(2) | >2.0 | 0.3 | 1.1 + 0.2 | 0.7 ± 0.2 | >2.0 | 0.4 | 1.5 + 0.3 | 0.5 ± 0.2 |
| CHLA-119 | >2.0 | 0.3 | 0.6 + 0.1 | 0.5 ± 0.2 | >2.0 | >0.4 | 0.9 + 0.2 | 0.2 ± 0.2 |
| CHLA-90 | >2.0 | 0.4 | 0.6 + 0.1 | 0.3 ± 0.1 | >2.0 | >0.4 | 0.5 + 0.3 | 0.2 ± 0.1 |
| CHLA-172 | 0.8 | 0.2 | 0.4 + 0.05 | 0.5 ± 0.3 | 2.0 | >0.4 | 0.6 + 0.1 | 0.4 ± 0.2 |
| p14 deletion | ||||||||
| LA-N-6 | >2.0 | 0.3 | 0.8 + 0.2 | 0.7 ± 0.3 | >2.0 | >0.4 | 1.5 + 0.3 | 0.4 ± 0.3 |
| Transfected clones | ||||||||
| CHLA-15EV | 1.0 + 0.2 | 2.0 + 0.4 | ||||||
| CHLA-15175a | 0.3 + 0.06 | 0.7 + 0.1 | ||||||
| CHLA-15175b | 0.6 + 0.1 | 1.0 + 0.2 | ||||||
| CHLA-20EV | >2.0 + >0.4 | >2.0 + >0.4 | ||||||
| CHLA-20273c | 1.0 + 0.2 | 2.0 + 0.4 | ||||||
| CHLA-20273d | 1.1 + 0.2 | 1.4 + 0.3 | ||||||
If 90% or 99% cytotoxicity was not achieved at the tested concentrations, then LC90 or LC99 values were reported as “> the highest tested concentration”. The highest concentrations tested were 2 μM for vorinostat, and 0.4 μM for flavopiridol. Similarly, if 90% or 99% cytotoxicity was achieved at concentrations lower than tested, then LC90 or LC99 values were reported as “< the lowest tested concentration”. The lowest concentrations tested were 0.025 μM for vorinostat, and 0.05 μM for flavopiridol.
The combination index (CI) correlates the cytotoxicity of drug combinations to the single-agent activities. Standard deviations (±) for CI values are also included.
CI was not determined (ND) if cytotoxicity was not achieved within the concentration range tested. Interpretation of CI values: 0.1–0.3 = strong synergism, >0.3 – 0.7 = synergism, >0.7–0.9 = slight synergism, >0.9 –1.0 = additive effect, more than 1.1 = antagonism.