Article
Attenuation of cell motility and invasion by treatment of U87 glioma cells with the nitric oxide donor JS-K in vitro
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Authors
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Stefanie Bette
- Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg, Germany
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Brunhilde Baumer
- Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg, Germany
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Astrid Weyerbrock
- Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg, Germany
| Published: | September 16, 2010 |
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Outline
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Objective: The diazeniumdiolate JS-K generates nitric oxide (NO) on enzymatic activation in GST-expressing cells. In addition to growth-inhibitory and chemosensitizing effects in tumors including U87 gliomas, JS-K has anti-invasive effects in breast cancer cells. The objective was to evaluate the anti-migratory effect of JS-K in U87 glioma cells in vitro.
Methods: Migration and invasion were assessed using cell motility and Boyden chamber assays. U87 cells were grown to confluence in 6-well plates separated by silicone walls. After removal of the walls they were treated with JS-K concentrations between 1–10µM. The distance between cell populations was measured after 6, 24, and 48h using Axiovision LE-software (Zeiss). To study invasion, 105 U87 cells were plated on inserts with 8µm pore-size polycarbonate filters coated with Matrigel (0,7mg/ml) and incubated for 24hours with JS-K (1–10µM). Cell migration was evaluated by counting five fields on each filter and expressed as the mean number of cells that had migrated through the filter. The experiments were repeated at least three times and analysed by ANOVA.
Results: JS-K significantly reduced the capacity of U87 cells to migrate towards each other and form a confluent monolayer in a cell motility assay at doses which did not affect viability. Migration across a matrigel-coated membrane was also significantly attenuated in a concentration-dependent manner at 5µM and 10µM, but not at 1 µM (p=0.0009 and p<0.0001, respectively).
Conclusions: This is the first report that the NO donor JS-K has anti-migratory effedtsoin U87 glioma cells in vitro. Effects on proliferation and migration and chemosensitizing properties make NO donors good candidates for multimodal cancer therapy.
