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

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Title Thiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress
Author Ito, Koichi; Scott, Stacy; Cutler, Samuel Joseph; Dong, Lan-feng; Neuzil, Jiri; Blanchard, Helen; Ralph, Stephen John
Journal Name Angiogenesis
Year Published 2011
Place of publication Netherlands
Publisher Springer
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 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.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1007/s10456-011-9213-5
Copyright Statement Copyright 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.
Volume 14
Issue Number 3
Page from 293
Page to 307
ISSN 1573-7209
Date Accessioned 2011-06-21
Date Available 2012-09-14T01:10:17Z
Language en_US
Research Centre Griffith Health Institute; Institute for Glycomics; Molecular Basis of Disease
Faculty Griffith Health Faculty
Subject Cancer Therapy (excl Chemotherapy and Radiation Therapy)
URI http://hdl.handle.net/10072/40730
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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