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Effects
of the 5-lipoxygenase inhibitors AA-863 and U-60,257 on human glioma cell lines
Gati
I, Bergstrom M, Csoka K, Muhr C, Carlsson J
Department
of Neurology, Uppsala University, Sweden
The
effects of two specific 5-lipoxygenase inhibitors AA-863 and U-60,257 (piriprost)
on the growth of two human glioma cell lines, U-343 MGa and U-251 MG were
investigated.
Both monolayer cultured cells and spheroids were studied.
The results of the monolayer studies showed potent and dose dependent inhibitory
effects on the proliferation of glioma cells (IC50/one week treatment/of AA-863:
9.0 microM, IC50 of U-60,257: 40.0 microM).
The experiments made on the tumor spheroids suggested an inhibitory effect on
proliferation and volume growth already at lower doses (AA-863: 0.4-2.0 microM,
U-60,257: 1.0-5.0 microM), a dose range where effects were not found in
monolayers.
At higher doses (AA-863: 10.0-30.0 microM, U-60,257: 30.0-90.0 microM) the
experiments with spheroids failed to demonstrate a further inhibitory effect on
spheroid volume, probably attributed to phenomena such as swelling of cells,
dissociation of spheroid structure and development of necrosis.
The clearly dose dependent inhibitory effect on the proliferation of human
glioma cells in monolayer culture and the inhibitory effects on spheroid growth
with these specific inhibitors indicate a role for lipoxygenase products in the
growth of gliomas.
PMID: 2117290 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2117290&dopt=Abstract
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