Cytotoxicity of ethonafide and other anticancer agents in the topoisomerase II knockdown cell lines Data are presented in micromolar and represent the mean ± S.E.M. of the IC50 of each agent after a 1- or 3-day exposure. The -fold resistance, compared with the average of the wild-type and transfected control cell lines, is shown in parentheses. Due to the low potency at short exposures, the IC50 values for XK469 and docetaxel were determined after a 3-day exposure to the respective agents.
Exposure Time | Agent | IC50 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Ethonafide | XK469 | Mitoxantrone | Melphalan | Docetaxel | ||||||
| μ M | ||||||||||
| 1 day | Wild type | 0.174 ± 0.010 | N.D. | 0.024 ± 0.001 | 137 ± 29.1 | N.D. | ||||
| Scramble control | 0.161 ± 0.039 | N.D. | 0.034 ± 0.005 | 129 ± 16.0 | N.D. | |||||
| shTIIα | 2.57 ± 0.27† (15.3) | N.D. | 1.09 ± 0.235† (37.6) | 129 ± 26.7 (0.97) | N.D. | |||||
| shTIIβ | 0.187 ± 0.052 (1.1) | N.D. | 0.036 ± 0.005 (1.2) | 154 ± 30.3 (1.2) | N.D. | |||||
| 3 day | Wild type | 0.027 ± 0.003 | 109 ± 11.5 | 0.0019 ± 3 × 10–4 | 8.9 ± 1.3 | 0.0019 ± 2 × 10–4 | ||||
| Scramble control | 0.027 ± 0.002 | 75.5 ± 6.52 | 0.0024 ± 1 × 10–4 | 9.16 ± 0.45 | 0.0029 ± 8 × 10–4 | |||||
| shTIIα | 0.103 ± 0.015† (3.8) | 224 ± 26.6* (2.4) | 0.0071 ± 0.001† (3.3) | 8.5 ± 0.67 (0.94) | 0.0025 ± 2 × 10–4 (1.0) | |||||
|
| shTIIβ | 0.046 ± 0.006 (1.7) | 508 ± 21.3† (5.5) | 0.0075 ± 4 × 10–4† (3.5) | 9.89 ± 1.16 (1.1) | 0.0039 ± 6 × 10–4 (1.6) | ||||
N.D., not determined
↵* Statistical significance was determined by an ANOVA followed by a Student-Newman-Keuls multiple comparisons test compared with wild-type cell line; p < 0.01
↵† Statistical significance was determined by an ANOVA followed by a Student-Newman-Keuls multiple comparisons test compared with wild-type cell line; p < 0.001