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  • Title: Toosendanin demonstrates promising antitumor efficacy in osteosarcoma by targeting STAT3.
    Author: Zhang T, Li J, Yin F, Lin B, Wang Z, Xu J, Wang H, Zuo D, Wang G, Hua Y, Cai Z.
    Journal: Oncogene; 2017 Nov 23; 36(47):6627-6639. PubMed ID: 28783167.
    Abstract:
    Signal transducer and activator of transcription 3(STAT3) is an emerging target for cancer therapy. In this study, we identify Toosendanin (TSN) is an effective inhibitor of STAT3, leading to the impediment of various oncogenic processes in osteosarcoma. TSN selectively inactivates phospho-STAT3 (Tyr-705); subsequent molecular docking and in vitro SPR analysis uncover TSN directly binds to the SH2 domain of STAT3. Consequently, TSN blocks STAT3 dimerization and impairs the complex formation of STAT3 and epidermal growth factor receptor (EGFR). In an animal tumor model study, TSN is well tolerated, inhibits osteosarcoma growth and metastasis. In another osteosarcoma patient-derived xenografts (PDX) model, we find TSN triggers strong inhibitory effects on patient-derived tumors. Further studies show that TSN also displays activity against other solid tumors. Our preclinical work therefore supports that TSN acts as a novel inhibitor of STAT3 that blocks tumorigenesis in ostoesarcoma.
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