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    LLL12B, a small molecule STAT3 inhibitor, induces growth arrest, apoptosis, and enhances cisplatin-mediated cytotoxicity in medulloblastoma cells

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    Author
    Chen, X.
    Pan, L.
    Wei, J.
    Zhang, R.
    Yang, X.
    Song, J.
    Bai, R.-Y.
    Fu, S.
    Pierson, C.R.
    Finlay, J.L.
    Li, C.
    Lin, J.
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    Date
    2021-03-22
    Journal
    Scientific Reports
    Publisher
    Nature Research
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1038/s41598-021-85888-x
    Abstract
    Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor and an oncogene product, which plays a pivotal role in tumor progression. Therefore, targeting persistent STAT3 signaling directly is an attractive anticancer strategy. The aim of this study is to test the efficacy of a novel STAT3 small molecule inhibitor, LLL12B, in suppressing medulloblastoma cells in vitro and tumor growth in vivo. LLL12B selectively inhibited the induction of STAT3 phosphorylation by interleukin-6 but not induction of STAT1 phosphorylation by INF-γ. LLL12B also induced apoptosis in human medulloblastoma cells. In addition, LLL12B exhibited good oral bioavailability in vivo and potent suppressive activity in tumor growth of medulloblastoma cells in vivo. Besides, combining LLL12B with cisplatin showed greater inhibition of cell viability and tumorsphere formation as well as induction of apoptosis comparing to single agent treatment in medulloblastoma cells. Furthermore, LLL12B and cisplatin combination exhibited greater suppression of medulloblastoma tumor growth than monotherapy in vivo. The present study supported that LLL12B is a novel therapeutic agent for medulloblastoma and the combination of LLL12B with a chemotherapeutic agent cisplatin may be an effective approach for medulloblastoma therapy. Copyright 2021, The Author(s).
    Sponsors
    This research was supported by the NIH/NINDS 1R01NS087213-01A1 Grant.
    Keyword
    LLL12B
    Cisplatin
    Medulloblastoma
    STAT3 Transcription Factor--antagonists & inhibitors
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15177
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-021-85888-x
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