A novel mechanism of action of the fumagillin analog, TNP-470, in the B16F10 murine melanoma cell line

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作者：

M Okr??J，W Kamysz，EM Slominska，A Mysliwski，J Bigda

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摘要：

TNP-470, a of , is an acknowledged inhibitor, presently undergoing clinical trials. It exerts an anti-proliferative effect directed against endothelial . This effect is known to be based on inhibition effected by the /pathway. We observed short-term toxicity of TNP-470 in the B16F10 line in vitro and investigated the mechanism of action. 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-protected B16F10 from TNP-470-induced 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 generation of ROS, which act toxically inside B16F10 . 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.

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关键词：

angiogenesis flow cytometry melanoma reactive oxygen species TNP-470

DOI：

10.1097/01.cad.0000172835.60142.a5

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年份：

2005