Artikel
Effect of a new drug. Vacquinol-1 on Glioblastoma cell lines
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Autoren
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Philip Sander
- Division of Experimental Anesthesiology, University Hospital Ulm, Ulm, Deutschland
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Haouraa Mostafa
- Division of Experimental Anesthesiology, University Hospital Ulm, Ulm, Deutschland
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Ayman Soboh
- Division of Experimental Anesthesiology, University Hospital Ulm, Ulm, Deutschland
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Andrej Pala
- Dept. of Neurosurgery, Bezirkskrankenhaus Günzburg, Günzburg, Deutschland
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C. Rainer Wirtz
- Dept. of Neurosurgery, Bezirkskrankenhaus Günzburg, Günzburg, Deutschland
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Alberto Catanese
- Institute for Cell Biology and Anatomy, Ulm University, Ulm, Deutschland
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Michael Georgieff
- Dept. of Anesthesiology, University Hospital Ulm, Ulm, Deutschland
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E. Marion Schneider
- Division of Experimental Anesthesiology, University Hospital Ulm, Ulm, Deutschland
| Veröffentlicht: | 9. Juni 2017 |
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Gliederung
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Objective: To evaluate the potential use of a novel chemotherapeutic drug called “Vacquinol-1” (Kitambi et al. 2014) against glioblastoma multiforme, we established a long-term cell culture system to address the kinetic activity.
Methods: Fresh tumor tissue was minced and trypsinized, then subjected to Ficoll-separation and culture using endotoxin-free fetal calf serum and Iscove’s modified essential medium. Permanent cell lines were established 4-8 weeks after culture initiation. Different concentrations of Vacquinol-1 were added to the cell culture and the effects of caspase 3/7 activation but lack of any other sign of apoptosis and viability were compared with the effect on stem cell lines derived from tooth pulpa cells.
Results: A concentration of 7 µM Vacquinol-1 resulted in significantly impaired growth characteristics of GBM cell lines as determined by IncuCyteZOOM assisted proliferation assays. Exogenous ATP lead to a dramatic salvage effect when it was titrated into the Vacquinol-1 assays. Titration of ATP revealed an optimum at 1-10 µM ATP. The effect was likely due to activation of the TRPM7 channel in GBM cells lines. To substantiate this finding, we tested the effect by 200 µM of Carvacrol, known to inhibit TRPM7 (Chen et al, 2015). Co-titration of Vacquinol-1, ATP and Carvacrol showed, that the sensitivity of Vacquinol-1 induced cell death in GBM derived cell lines could be increased by Carvacrol.
Conclusion: At 7 µM, Vacquinol-1 induced a rapid cell death in all GBM cell lines, occurring with massive cell blebbing. Morphological criteria of Vacquinol-induced cell death demonstrate that cell death is not related to apoptosis despite of caspase 3/7 activation. The effect of Vacquinol-1 was sensitive to neutralization by low concentrations of ATP, likely to activate TRPM7 channels. The effect by carvacrol on TRPM7 is the current target of further investigations.
