Setting up of an original computer-assisted methodology to characterize in vitro drug-induced anti-angiogenic effects.
The development of angiogenesis within a tumor brings on a sequence of extremely complex molecular events. We have developed a methodology which enables a wide set of biological parameters to be quantitatively determined in the field of anti-angiogenesis pharmacology. This methodology which includes a video cell tracking device, is unique because it offers the possibility of evaluating the specific influence of a given compound with potential anti-angiogenic properties on cell cycle kinetics, cell death, global cell line growth, and cell motility. We chose TNP-470, a synthetic analogue of fumagilin, to test our methodology on HUVEC cell lines taken from various human umbilical cord veins. The experiments carried out with TNP-470 did not confirm all the data reported in the literature. Our results show that i) TNP-470 could be considered as a cytotoxic agent; ii) this compound had an apparently marginal cytostatic effect; and iii) it did not increase the apoptosis level. Our methodology also revealed that the HUVEC cell lines are very heterogeneous in terms of different biological parameters. This highlights the problem of the reproductibility of the result.
Farinelle
S
S
Laboratoire d'Histologie, Faculté de Medecine, Université Libre de Bruxelles, Brussels, Belgium.
Dehauwer
C
C
Darro
F
F
Decaestecker
C
C
Fontaine
J
J
Pasteels
J L
JL
Van Ham
P
P
Atassi
G
G
Kiss
R
R
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001681:Biological Assay / Q000295:instrumentation / Q000379:methods; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement; D003510:Cyclohexanes / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D009389:Neovascularization, Pathologic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol