Effects of the 5-lipoxygenase inhibitors AA-863 and U-60,257 on human glioma cell lines

Prostaglandins, Leukotrienes, and Essential Fatty Acids
I GátiJ Carlsson

Abstract

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.

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Citations

Sep 1, 1992·Prostaglandins, Leukotrienes, and Essential Fatty Acids·M Fukushima
Jan 15, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Jennifer L WalkerYing-Yi Zhang
Apr 25, 2003·Cancer Control : Journal of the Moffitt Cancer Center·Ivo W Tremont-Lukats, Mark R Gilbert
Mar 17, 1993·Biochimica Et Biophysica Acta·Y V Kiran KumarP Reddanna

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