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Inhibition of Sonic Hedgehog Signaling Pathway by Thiazole Antibiotic Thiostrepton Attenuates the

Na Yang, Tai-Cheng Zhou, Xiu-xia Lei

    Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
    |March 11, 2016
    PubMed
    Abstract

    Insights

    Thiostrepton, an antibiotic, effectively reduces triple-negative breast cancer (TNBC) stem cells by inhibiting the sonic hedgehog (SHH) signaling pathway. This study highlights thiostrepton as a potential therapeutic agent for TNBC.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Pharmacology

    Background:

    • Triple-negative breast cancer (TNBC) lacks effective targeted therapies and endocrine treatments.
    • Identifying novel therapeutic targets and agents for TNBC is a critical clinical need.
    • Thiostrepton, a thiazole-containing antibiotic, was investigated for its anti-cancer effects on TNBC.

    Purpose of the Study:

    • To explore the cytostatic effect of thiostrepton on TNBC cell lines.
    • To investigate the molecular mechanisms underlying thiostrepton's action.
    • To determine if thiostrepton targets the sonic hedgehog (SHH) signaling pathway.

    Main Methods:

    • Cell viability assessed using MTT assay.
    • Cell surface markers monitored by flow cytometry (FCM).
    • Protein expression levels evaluated via Western blot analysis.

    Main Results:

    • Thiostrepton significantly suppressed the CD44+/CD24- stem-like cell population and sphere formation in TNBC cell lines.
    • Thiostrepton was demonstrated to target the sonic hedgehog (SHH) signaling pathway, repressing SHH ligand expression and reducing Gli-1 nuclear localization.
    • Downstream targets of the SHH pathway showed dose-dependent mRNA reduction post-thiostrepton treatment, confirming SHH ligand's role in maintaining stem-like populations.

    Conclusions:

    • Thiostrepton inhibits the CD44+/CD24- stem-like population in TNBC by suppressing the SHH signaling pathway.
    • This study provides novel insights into thiostrepton's anti-tumor mechanisms.
    • Thiostrepton emerges as a promising therapeutic candidate targeting the hedgehog signaling pathway in TNBC.

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