Novel STAT3 Phosphorylation Inhibitors Exhibit Potent Growth-Suppressive Activity in Pancreatic and Breast Cancer Cells

摘要: The constitutive activation of signal transducer and activator transcription 3 (STAT3) is frequently detected in most types human cancer where it plays important roles survival, drug resistance, angiogenesis, other functions. Targeting STAT3 signaling thus an attractive therapeutic approach for these cancers. We have recently developed novel small-molecule inhibitors, known as FLLL31 FLLL32, which are derived from curcumin (the primary bioactive compound turmeric). These compounds designed to bind selectively Janus kinase 2 the Src homology-2 domain, serve crucial dimerization transduction. Here we show that FLLL32 effective inhibitors phosphorylation, DNA-binding activity, transactivation vitro, leading impediment multiple oncogenic processes induction apoptosis pancreatic breast cell lines. also inhibit colony formation soft agar invasion exhibit synergy with anticancer doxorubicin against cells. In addition, can phosphorylation by IFNalpha interleukin-6 administration tumor growth vascularity chicken embryo xenografts well substantially reduce volumes mouse xenografts. Our findings highlight potential new their efficacy targeting cancers signaling.