Table 1.
Antiproliferative effects of the Janus compounds 1–4. The effects of the compounds on the inhibition of cancer cell proliferation were evaluated using the SRB assay in MDA-MB-435 cells and in isogenic pairs of cell lines that are sensitive or resistant to paclitaxel, respectively. The WT βIII cell line is a βIII-tubulin expressing subline of HeLa and the SK-OV-3-MDR-1/M6/6 is a P-glycoprotein expressing subline of SK-OV-3 cells. The IC50 (concentration that inhibits growth 50%) values were calculated from the linear portions of log dose–response curves. The relative resistance (Rr) was determined by dividing the IC50 of the resistant cell line by the IC50 of the parental cell line for each isogenic cell line pair. Paclitaxel (PTX) and CA-4 were used as positive controls. n = 3 ± SD.
| Compound (μM) | MDA-MB-435 | HeLa | WT βIII | Rr | SK-OV-3 | SK-OV-3-MDR-1/M6/6 | Rr |
|---|---|---|---|---|---|---|---|
| 1 | 6.5 ± 0.3 | 1.4 ± 0.2 | 5.4 ± 0.2 | 3.9 | 5.4 ± 0.8 | 7.4 ± 1.0 | 1.4 |
| 2 | 3.0 ± 0.3 | 2.4 ± 0.1 | 2.7 ± 0.2 | 1.1 | 2.5 ± 0.1 | 3.1 ± 0.2 | 1.2 |
| 3 | 4.2 ± 0.5 | 2.4 ± 0.4 | 4.6 ± 0.1 | 1.9 | 5.0 ± 0.4 | 5.4 ± 0.03 | 1.1 |
| 4 | 4.2 ± 0.5 | 3.5 ± 0.1 | 3.4 ± 0.1 | 1.0 | 4.1 ± 1.0 | 4.7 ± 0.5 | 1.1 |
| PTX (nM) | 4.5 ± 0.5 | 2.8 ± 0.4 | 24 ± 3.0 | 8.6 | 5.0 ± 0.6 | 1,200 ± 60 | 240 |
| CA-4 (nM) | 4.4 ± 0.5 | 3.3 ± 0.4 | 3.3 ± 0.3 | 1.0 | 5.5 ± 0.5 | 7.2 ± 1.1 | 1.3 |