dc.contributor.author | Ito, Koichi | |
dc.contributor.author | Scott, Stacy A | |
dc.contributor.author | Cutler, Samuel | |
dc.contributor.author | Dong, Lan-Feng | |
dc.contributor.author | Neuzil, Jiri | |
dc.contributor.author | Blanchard, Helen | |
dc.contributor.author | Ralph, Stephen J | |
dc.date.accessioned | 2017-05-03T15:27:24Z | |
dc.date.available | 2017-05-03T15:27:24Z | |
dc.date.issued | 2011 | |
dc.date.modified | 2012-09-14T01:10:17Z | |
dc.identifier.issn | 0969-6970 | |
dc.identifier.doi | 10.1007/s10456-011-9213-5 | |
dc.identifier.uri | http://hdl.handle.net/10072/40730 | |
dc.description.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. | |
dc.description.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.format.extent | 584232 bytes | |
dc.format.mimetype | application/pdf | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Springer | |
dc.publisher.place | Netherlands | |
dc.relation.ispartofstudentpublication | N | |
dc.relation.ispartofpagefrom | 293 | |
dc.relation.ispartofpageto | 307 | |
dc.relation.ispartofissue | 3 | |
dc.relation.ispartofjournal | Angiogenesis | |
dc.relation.ispartofvolume | 14 | |
dc.rights.retention | Y | |
dc.subject.fieldofresearch | Clinical sciences | |
dc.subject.fieldofresearch | Cancer therapy (excl. chemotherapy and radiation therapy) | |
dc.subject.fieldofresearch | Pharmacology and pharmaceutical sciences | |
dc.subject.fieldofresearch | Biochemistry and cell biology | |
dc.subject.fieldofresearchcode | 3202 | |
dc.subject.fieldofresearchcode | 321104 | |
dc.subject.fieldofresearchcode | 3214 | |
dc.subject.fieldofresearchcode | 3101 | |
dc.title | Thiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.faculty | Griffith 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.issued | 2011 | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Neuzil, Jiri | |
gro.griffith.author | Ralph, Stephen J. | |