Table 4.
Activity* of compound 7, 8, 11, 13, and 14 against cancer-related signaling pathways in T98G glioblastoma multiforme cells.#
| Compounds | Stat3/IL-6 | Smad /TGF-beta | Ap-1/PMA | NF-kB/PMA | E2F/PMA | Myc/PMA | Ets/PMA | Notch/PMA | FoxO | Wnt/m-wnt 3a | Hdghog/PMA | miR-21 | pTK | Ras | AhR |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 7 | 8.99 | 10.5 | - | - | < 5 | 7.55 | - | 12.6 | - | 2.5 | 5.3 | 18.9 | - | - | - |
| 8 | 4.9 | 3.5 | 10.25 | 7.66 | 4.5 | 5.7 | 7.3 | < 5 | - | 12.1 | 7.0 | - | - | 7.0 | 2.0 |
| 11 | 18.3 | 21 | 21 | 18.6 | 5.7 | 10.2 | > 20 | 10.59 | - | 15.9 | 13.79 | - | - | 13.78 | |
| 13 | 6.55 | 9.95 | 10.89 | 16.9 | 4.9 | 4.8 | 11.44 | < 5 | - | 7.44 | - | 11.87 | - | 11.13 | - |
| 14 | 4.33 | 2.17 | 4.45 | 4.8 | 4.43 | 1.86 | 4.7 | 2.12 | 13.7 | 9.11 | 8.35 | - | - | 6.5 | 7.4 |
* Values are IC50 in µM that inhibited luciferase induction by 50%. Test agents were added to cells 30 min before the addition of the indicated inducer and were harvested 4 or 6 h later for the luciferase assay (Notch, FoxO, Wnt, Hedgehog, miR-21). No inducer was added to cells transfected with the FoxO, miR-21, or pTK control vector.# This unique assay panel had a special feature of evaluating which pathways were sensitive (modulated) to a test agent. Each test agent was run at various concentrations and each concentration was tested in duplicate. As this multiplex assay offered many advantages for the simultaneous measurement and analysis of multiple pathways for any test agent, the intra- and inter-assay precision, accuracy, and reproducibility were high with this method. The results were normalized to the control vector, which was pTK. This empty vector control allowed us to see any non-specific cytotoxic effects of the test compounds on the cells. -: No activity detected.