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A novel mechanism o...
A novel mechanism of action of the fumagillin analog, TNP-470, in the B16F10 murine melanoma cell line
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- Okroj, Marcin (author)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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Kamysz, Wojciech (author)
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Slominska, Ewa M (author)
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Mysliwski, Andrzej (author)
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Bigda, Jacek (author)
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(creator_code:org_t)
- 2005
- 2005
- English.
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In: Anti-Cancer Drugs. - 0959-4973. ; 16:8, s. 817-823
- Related links:
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https://lup.lub.lu.s...
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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