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dc.contributor.authorIto, Koichi
dc.contributor.authorScott, Stacy A
dc.contributor.authorCutler, Samuel
dc.contributor.authorDong, Lan-Feng
dc.contributor.authorNeuzil, Jiri
dc.contributor.authorBlanchard, Helen
dc.contributor.authorRalph, Stephen J
dc.date.accessioned2017-05-03T15:27:24Z
dc.date.available2017-05-03T15:27:24Z
dc.date.issued2011
dc.date.modified2012-09-14T01:10:17Z
dc.identifier.issn0969-6970
dc.identifier.doi10.1007/s10456-011-9213-5
dc.identifier.urihttp://hdl.handle.net/10072/40730
dc.description.abstractCancer 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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent584232 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer
dc.publisher.placeNetherlands
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom293
dc.relation.ispartofpageto307
dc.relation.ispartofissue3
dc.relation.ispartofjournalAngiogenesis
dc.relation.ispartofvolume14
dc.rights.retentionY
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchCancer therapy (excl. chemotherapy and radiation therapy)
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode321104
dc.subject.fieldofresearchcode3214
dc.subject.fieldofresearchcode3101
dc.titleThiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Medical Science
gro.rights.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.
gro.date.issued2011
gro.hasfulltextFull Text
gro.griffith.authorNeuzil, Jiri
gro.griffith.authorRalph, Stephen J.


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