A novel mechanism of action of the fumagillin analog, TNP-470, in the B16F10 murine melanoma cell line
(2005) In Anti-Cancer Drugs 16(8). p.817-823- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1132307
- author
- Okroj, Marcin LU ; Kamysz, Wojciech ; Slominska, Ewa M ; Mysliwski, Andrzej and Bigda, Jacek
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Anti-Cancer Drugs
- volume
- 16
- issue
- 8
- pages
- 817 - 823
- publisher
- Rapid Communications
- external identifiers
-
- pmid:16096429
- scopus:24044502878
- ISSN
- 0959-4973
- language
- English
- LU publication?
- yes
- id
- f6ae6aaf-dadd-42d2-adb6-064c54d69557 (old id 1132307)
- date added to LUP
- 2016-04-01 12:23:11
- date last changed
- 2022-01-27 02:59:52
@article{f6ae6aaf-dadd-42d2-adb6-064c54d69557,
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.}},
author = {{Okroj, Marcin and Kamysz, Wojciech and Slominska, Ewa M and Mysliwski, Andrzej and Bigda, Jacek}},
issn = {{0959-4973}},
language = {{eng}},
number = {{8}},
pages = {{817--823}},
publisher = {{Rapid Communications}},
series = {{Anti-Cancer Drugs}},
title = {{A novel mechanism of action of the fumagillin analog, TNP-470, in the B16F10 murine melanoma cell line}},
volume = {{16}},
year = {{2005}},
}