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

0369512 - BTÚ 2012 RIV NL eng J - Článek v odborném periodiku
Ito, K. - Scott, S.A. - Cutler, S. - Dong, L.-F. - Neužil, Jiří - Blanchard, H. - Ralph, S.J.
Thiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress.
Angiogenesis. Roč. 14, č. 3 (2011), s. 293-307. ISSN 0969-6970. E-ISSN 1573-7209
Výzkumný záměr: CEZ:AV0Z50520701
Klíčová slova: Galectin-1 inhibitor * oxidative stress * angiogenesis
Kód oboru RIV: FD - Onkologie a hematologie
Impakt faktor: 6.063, rok: 2011

Cancer cells produce galectin-1 as a tumor promoting protein. Thiodigalactoside (TDG) as a non-metabolised drug, is shown to suppress tumor growth by inhibiting cancer enhancing activities of galectin-1, including immune cell dysregulation, angiogenesis and protection against oxidative stress. Using B16F10 melanoma and 4T1 orthotopic breast cancer models, intratumoral injection of TDG significantly raised the levels of infiltrating CD8(+) lymphocytes and reduced CD31(+) endothelial cell content, reducing tumor growth. TDG treatment of tumors in Balb/c nude mice reduced angiogenesis and slowed tumor growth by a third less than in immunocompetent mice. Knocking down galectin-1 expression (G1KD) significantly impeded tumor growth and the sensitivity of the G1KD tumors to TDG was severely reduced. Endothelial cells were protected by galectin-1 from oxidative stress-induced apoptosis, but TDG inhibited this antioxidant protective effect of galectin-1 and reduced tube forming activity.
Trvalý link: http://hdl.handle.net/11104/0203559