Pro-apoptotic properties of morphine in neuroblastoma × glioma NG108-15 hybrid cells: modulation by yohimbine
Article first published online: 12 SEP 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 34, Issue 1, pages 19–24, January 2014
How to Cite
Polanco, M. J., Alguacil, L. F. and González-Martín, C. (2014), Pro-apoptotic properties of morphine in neuroblastoma × glioma NG108-15 hybrid cells: modulation by yohimbine. J. Appl. Toxicol., 34: 19–24. doi: 10.1002/jat.2817
- Issue published online: 29 OCT 2013
- Article first published online: 12 SEP 2012
- Manuscript Accepted: 6 AUG 2012
- Manuscript Revised: 27 JUL 2012
- Manuscript Received: 11 JUL 2012
Short-term incubation with pharmacologically relevant concentrations of morphine has been shown to transiently affect the metabolism and redox status of NG108-15 cells through δ-opioid receptor stimulation, but apparently did not provoke cell death. The present work tries to determine if incubation with morphine at longer time intervals (24 h) provokes apoptosis and/or necrosis, as it has been described in other cell lines. We have also checked the potential modulatory role of yohimbine on these effects, on the basis of the previously described interactions between this drug and opioid receptor ligands. Incubation with morphine 0.1 and 10 μM provoked the appearance of images compatible with apoptosis (bebbling, pyknotic cells with cytoplasmic and nuclear condensation) and necrosis (cells swollen with vacuolated cytoplasm lacking cell processes) that could be observed directly and/or after staining with methylene blue, crystal violet and propidium iodide/4',6-diamidino-2-phenylindole (IP/DAPI). Quantification of apoptosis by activation of caspases 3 and 7 and DNA fragmentation with the Tunel assay revealed a modest but significant increase after incubation with the two concentrations of morphine used. Co-incubation with 10 μM yohimbine prevented all these effects of the opioid. The results extend previous findings of a yohimbine-sensitive, neurotoxic effect of morphine on NG108-15 cells. Copyright © 2012 John Wiley & Sons, Ltd.