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Figure 4 | Breast Cancer Research

Figure 4

From: Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells

Figure 4

SHP-1-dependent inhibition of STAT3 mediates the apoptotic effects of SC-1 and SC-43 in breast cancer cells. A, inhibition of SHP-1 reverses effects of SC-1 and SC-43 on apoptosis. MDA-MB-468 cells were pretreated with 50 μM sodium vanadate, a non-specific phosphatase inhibitor (Left), or 50 μM PTP inhibitor III, a specific SHP-1 inhibitor (Right), for 60 minutes and then treated with SC-1 or SC-43 at 7.5 μM for 36 hours. B, silencing SHP-1 by siRNA reduces the effects of SC-1 and SC-43 on p-STAT3 inhibition and apoptosis in MDA-MB-453 and MDA-MB-468 cells. Cells were transfected with control siRNA (scrambled) or SHP-1 siRNA for 48 hours then treated with SC-1 or SC-43 at 7.5 μM for another 24 hours. C, effects of sorafenib, SC-1 and SC-43 on SHP-1 expression and phosphorylation (Tyr536 and Ser591). MDA-MB-468 cells were exposed to sorafenib, SC-1 or SC-43 at 7.5 μM for 36 hours. Western blot data are representative of three independent experiments. D , the activity of SHP-1 (Upper) and SHP-2 (Lower) in drug-treated MDA-MB-468 cells. Cells were treated with sorafenib, SC-1 or SC-43 at 7.5 μM for 36 hours and cell lysates were assayed for phosphatase activity as described in Methods. E, dose-escalation effects of SC-43 on the activity of SHP-1 (Upper) and SHP-2 (Lower) in drug-treated MDA-MB-468 cells. Cells were treated with SC-43 at the indicated doses for 36 hours. F, effect of SC-43 on SHP-1 activity in drug-treated HCC-1937, MDA-MB-231, MCF-7, MDA-MB-453 and SK-BR3 cells (Upper); cells were treated with SC-43 at 10 μM for 36 hours. Effects of sorafenib, SC-1 and SC-43 on phosphatase activity in recombinant SHP-1 protein (Lower). Recombinant SHP-1 protein (25 ng) was incubated with drugs at 100 nM for 30 minutes. For bar charts, Columns, mean; bars, SD (n = 3). *P <0.05.

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