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  • Thiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress

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    Author(s)
    Ito, Koichi
    Scott, Stacy A
    Cutler, Samuel
    Dong, Lan-Feng
    Neuzil, Jiri
    Blanchard, Helen
    Ralph, Stephen J
    Griffith University Author(s)
    Neuzil, Jiri
    Ralph, Stephen J.
    Year published
    2011
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    Abstract
    Cancer cells produce galectin-1 as a tumor promoting protein. Thiodigalactoside (TDG) as a non-metabolised small drug, is shown to suppress tumor growth by inhibiting multiple cancer enhancing activities of galectin-1, including immune cell dysregulation, angiogenesis and protection against oxidative stress. Thus, using B16F10 melanoma and 4T1 orthotopic breast cancer models, intratumoral injection of TDG significantly raised the levels of tumor-infiltrating CD8+ lymphocytes and reduced CD31+ endothelial cell content, reducing tumor growth. TDG treatment of tumors in Balb/c nude mice (defective in T cell immunity) reduced ...
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    Cancer cells produce galectin-1 as a tumor promoting protein. Thiodigalactoside (TDG) as a non-metabolised small drug, is shown to suppress tumor growth by inhibiting multiple cancer enhancing activities of galectin-1, including immune cell dysregulation, angiogenesis and protection against oxidative stress. Thus, using B16F10 melanoma and 4T1 orthotopic breast cancer models, intratumoral injection of TDG significantly raised the levels of tumor-infiltrating CD8+ lymphocytes and reduced CD31+ endothelial cell content, reducing tumor growth. TDG treatment of tumors in Balb/c nude mice (defective in T cell immunity) reduced angiogenesis and slowed tumor growth by a third less than in immunocompetent mice. Knocking down galectin-1 expression (G1KD) in both cancer cell types significantly impeded tumor growth and the sensitivity of the G1KD tumors to TDG was severely reduced, highlighting a specific role for galectin-1. Endothelial cells were protected by galectin-1 from oxidative stress-induced apoptosis induced by H2O2, but TDG inhibited this antioxidant protective effect of galectin-1 and reduced tube forming activity in angiogenic assays. We show for the first time that the single agent, TDG, concurrently prevents many tumor promoting effects of galectin-1 on angiogenesis, immune dysregulation and protection against oxidative stress, providing a potent and novel small molecule as an anti-cancer drug.
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    Journal Title
    Angiogenesis
    Volume
    14
    Issue
    3
    DOI
    https://doi.org/10.1007/s10456-011-9213-5
    Copyright Statement
    © 2011 Springer Netherlands. This is an electronic version of an article published in Apoptosis, 2011. Apoptosis is available online at: http://www.springerlink.com/ with the open URL of your article.
    Subject
    Clinical sciences
    Cancer therapy (excl. chemotherapy and radiation therapy)
    Pharmacology and pharmaceutical sciences
    Biochemistry and cell biology
    Publication URI
    http://hdl.handle.net/10072/40730
    Collection
    • Journal articles

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