Levamisole inhibits angiogenesis in vitro and tumor growth in vivo.
The synthetic anthelmintic compound Levamisole has previously been used in cancer treatment as an adjuvant in combination with 5-fluorouracil. Its mode of action remains unclear, but an immune-stimulatory effect has been suggested. Here, we show that Levamisole inhibits angiogenesis in vitro and tumor growth in vivo. In vitro, Levamisole specifically inhibits proliferation and differentiation of endothelial cells propagated in co-culture with fibroblasts. In vivo, Levamisole inhibits the growth in nude mice of a transplanted human tumor. The use of nude mice as tumor hosts permits the discrimination between the angiogenesis inhibitory effect of Levamisole and its assumed immune-stimulatory effect. Our findings support a possible therapeutic effect of angiogenesis inhibitors in the treatment of cancer and call for further investigations of the mechanism(s) underlying the anti-angiogenic effect of Levamisole.
Friis
Tina
T
Department of Research and Development, Division of Plasma Products, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark.
Engel
Anne-Marie
AM
Klein
Bjarke Mirner
BM
Rygaard
Jørgen
J
Houen
Gunnar
G
D000230:Adenocarcinoma / Q000188:drug therapy*; D000276:Adjuvants, Immunologic; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007978:Levamisole / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D014471:Umbilical Veins / Q000166:cytology; D023041:Xenograft Model Antitumor Assays
D000276:Adjuvants, Immunologic; D020533:Angiogenesis Inhibitors; D007978:Levamisole