Figure 1

SC-1 and SC-43, without effects on raf-1 kinase activity, show more potent anti-proliferative activity than sorafenib in breast cancer cells. A, chemical structures of sorafenib, SC-1 and SC-43. B, effects of sorafenib, SC-1 and SC-43 on Raf-1 activity in MDA-MB-231 cells. Columns, mean (n = 3); bars, SD; *P <0.05 compared to control. C , effects of sorafenib, SC-1 and SC-43 on the phosphorylation of ERK1/2, VEGFR2 and PDGFRβ in MDA-MB-231cells. Cells were exposed to sorafenib, SC-1 or SC-43 at 1 and 5 μM for 12 hours. Data are representative of three independent experiments. D, effects of sorafenib, SC-1 and SC-43 on the phosphorylation of STAT3 upstream kinases JAK1 and JAK2 in MDA-MB-231 (Left) and MDA-MB-468 cells (Right). Cells were exposed to sorafenib, SC-1 or SC-43 at 1 and 5 μM for 12 hours. Data are representative of three independent experiments. E, dose-escalation effects of sorafenib, SC-1 and SC-43 on cell viability in six breast cancer cell lines. Cells were exposed to sorafenib, SC-1 or SC-43 at the indicated doses for 48 hours and cell viability was assessed by the MTT assay. Points, mean (n = 3); bars, SD. MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.