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• W2066778538 abstract "TNP-470, a semisynthetic derivative of fumagillin, is an acknowledged angiogenesis inhibitor, presently undergoing clinical trials. It exerts an anti-proliferative effect directed against endothelial cells. This effect is known to be based on cell cycle inhibition effected by the p53/p21 pathway. We observed short-term toxicity of TNP-470 in the B16F10 murine melanoma cell line in vitro and investigated the mechanism of action. Cell death occurred as soon as 2 h after the addition of TNP-470, without typical apoptotic features. The toxic effect could be modulated and it depended on the type of culture medium or supplementation with anti-oxidants. Addition of N-acetylcysteine protected B16F10 cells from TNP-470-induced death and inhibited an increase in the generation of reactive oxygen species (ROS), which are detected by the 2',7'-dichlorodihydrofluorescein diacetate probe. We conclude that TNP-470 can induce intracellular generation of ROS, which act toxically inside B16F10 cells. One may suggest that this novel activity of TNP-470 might be beneficial in some cases, but it could also be responsible for some undesirable side-effects. The possibility of its modulation gives a prospect for controlling the action of this potential drug and probably its derivatives." @default.
• W2066778538 created "2016-06-24" @default.
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• W2066778538 date "2005-09-01" @default.
• W2066778538 modified "2023-09-24" @default.
• W2066778538 title "A novel mechanism of action of the fumagillin analog, TNP-470, in the B16F10 murine melanoma cell line" @default.
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• W2066778538 doi "https://doi.org/10.1097/01.cad.0000172835.60142.a5" @default.
• W2066778538 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16096429" @default.
• W2066778538 hasPublicationYear "2005" @default.
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