Table II.
Effects of VPA on clofarabine cytotoxicities in pediatric AML cell lines and diagnostic AML blasts
| Cell line/Patient | VPA IC50 (mM) | Clofarabine IC50 (nM) | p value | |||||
|---|---|---|---|---|---|---|---|---|
| 0 mM VPA | 0.15 mM VPA | 0.3 mM VPA | 0.5 mM VPA | 0.75 mM VPA | 1.0 mM VPA | |||
| MV4-11 | 0.7±0.1 | 29.4±0.6 | 21.5±0.6 (0.9) | 16.0±0.3 (1.0) | 6.9±0.4 (1.0) | ND | ND | <0.008 |
| Kasumi-1 | 0.9±0.1 | 49.0±3.7 | 35.0±3.1 (0.9) | 23.6±5.6 (0.8) | 11.6±1.5 (0.9) | ND | ND | <0.014 |
| CMS | 2.7±0.2 | 14.4±0.4 | ND | ND | 13.1±0.3 (1.0) | 12.5±0.8 (1.0) | 11.0±0.9 (1.0) | NS |
| THP-1 | 3.3±0.1 | 33.2±0.5 | ND | ND | 30.5±1.0 (1.0) | 29.5±0.3 (1.1) | 28.8±1.1 (1.1) | NS |
| A30307 | 1.1 | 18.2 | ND | ND | 1.2 (0.5) | 0.8 (0.6) | ND | NA |
| A30308 | 4.9 | 337.8 | ND | ND | 259.0 (0.9) | 191.1 (0.7) | 148.3 (0.6) | NA |
| A30309 | 2.0 | 129.3 | ND | ND | 78.02 (0.8) | 52.2 (0.9) | 40.0 (0.8) | NA |
| A30310 | 1.7 | 38.9 | ND | ND | 22.2 (0.7) | 12.8 (0.6) | 13.2 (0.7) | NA |
| A30311 | 0.9 | 67.6 | ND | ND | 12.6 (0.8) | 4.4 (0. 9) | ND | NA |
| A30110 | 1.0 | 55.9 | ND | ND | 7.5 (0.6) | 3.2 (0.7) | ND | NA |
| A30207 | 0.7 | 36.8 | ND | ND | 2.0 (0.8) | ND | ND | NA |
| A30224 | 0.7 | 136.8 | 46.6 (0.5) | 12.1 (0.5) | 5.9 (0.7) | ND | ND | NA |
| A30230 | 0.2 | 189.1 | 3.6 (0.9) | ND | ND | ND | ND | NA |
Note: For individual drug treatments, pediatric AML cells were treated with variable concentrations of clofarabine (0–1 μM) or VPA (0– 8 μM) for 72h; for combined treatments, the cells were treated with variable concentrations of clofarabine (0– 1μM) in combination with VPA (0–1 mM) for 72h. Viable cells were measured by using the MTT reagent and a visible microplate reader. Clofarabine and VPA IC50s are presented as mean ± standard errors from at least three independent experiments for the pediatric AML cell lines, while those for the diagnostic AML blasts are presented as mean of duplicates from one experiment. Numbers in parentheses represent the combination index values. NA, not applicable; NS, not significant; ND, not determined.