Abstract
In vivo studies have suggested a role for cyclooxygenase inhibitors in the control of tumor metastases. As cyclooxygenase inhibition may increase the production of lipoxygenase products of AA metabolism we investigated the effect of the lipoxygenase derivatives 12-Hydroxyeicosatetraenoic acid (12-HETE) and 15-Hydroxyeicosatetraenoic acid (15-HETE) on tumor cell proliferation in vitro. To prepare 12-HETE, human platelets were incubated with AA in the presence of indomethacin. 15-HETE was prepared from soybean lipoxygenase. The material was purified by column chromatography and reverse phase HPLC. Identity and purity were confirmed by GC-MS. Neuroblastoma cells in tissue culture (SK-N-SH) were incubated in serum free RPMI-1640 or this media with 12-HETE, 15-HETE or AA. 12-HETE at concentrations at 20 μM, 30 μM and 50 μM induced respectively 16.3 ± 3.8% (lSE), 32.0 ± 4.4% and 63.6±4.2% inhibition of 3H-thymidine incorporation compared to control (p<.01). 15-HETE at the same concentrations produced inhibitions of 14.5±7.7%, 20.9 ± 2.8% and 46.1±12.1% respectively (p <.01). AA had no effect. At higher concentrations (30 and 50 μM) 12HETE produced a greater effect than 15HETE. When evaluated in the presence of serum, 12-HETE (120 μM) produced a 20.6±2.8% inhibition of the increase in total DNA content over 48 hours, while 15-HETE (120 μM) produced a 16.5±5.3% inhibition. We conclude that 12-HETE, the product of platelet lipoxygenase, and 15-HETE, a product of neutrophil and monocyte lipoxygenase inhibit human neuroblastoma cell growth in vitro and may play a role in modulating tumor proliferation in vivo.
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Werner, E., Walenga, R., Dubowy, R. et al. LIPOXYGENASE PRODUCTS OF ARACHIDONIC ACID (AA) METABOLISM INHIBIT PROLIFERATION OF HUMAN NEUROBLASTOMA CELLS IN VITRO. Pediatr Res 18 (Suppl 4), 251 (1984). https://doi.org/10.1203/00006450-198404001-00947
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DOI: https://doi.org/10.1203/00006450-198404001-00947