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Copper accumulation and acute toxicity in C6 glioma cells after application of copper oxide nanoparticles

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conference contribution
posted on 2017-08-01, 00:00 authored by A Joshi, W Rastedt, K Faber, Aaron SchultzAaron Schultz, F Bulcke, R Dringen
The rat C6 glioma cell-line is frequently used as an experimental
model for glial tumors. To investigate the potential use of copper
oxide nanoparticles (CuO-NPs) as a therapeutic drug for glioma
treatment, the consequences of an application of CuO-NPs on the
cellular copper content and cell viability of C6 glioma cells was
investigated. CuO-NPs were synthesized by a wet-chemical method
and were coated with dimercaptosuccinic acid and bovine serum
albumin to improve colloidal stability in physiological media.
Application of these protein-coated nanoparticles (pCuO-NPs) to
C6 cells caused a strong time-, concentration- and temperaturedependent
copper accumulation. This cellular copper accumulation
was accompanied by severe toxicity as indicated by the loss in cellular
MTT-reduction capacity, the loss in cellular LDH activity, and by an
increase in the number of propidium iodide-positive cells. Toxicity of
pCuO-NPs to C6 cells was only observed for incubation conditions
that increased the specific cellular copper contents above 20 nmol
copper per mg protein. Despite severe toxicity, no obvious formation
of reactive oxygen species was found in pCuO-NP-treated C6 cells.
Unexpectedly, C6 glioma cells were less vulnerable to pCuO-NPs
than cultured primary brain astrocytes. Both cellular copper accumulation
and pCuO-NP-induced toxicity in C6 cells were prevented by
application of cell membrane-permeable and -impermeable copper
chelators, but not by frequently used endocytosis inhibitors. These
data suggest that uptake of copper ions liberated extracellularly from
the pCuO-NPs, rather than uptake of intact pCuO-NPs, leads to the
observed toxicity of pCuO-NP-treated glioma cells.



International Society of Neurochemistry (ISN) and the European Society for Neurochemistry (ESN) : Bienniel Meeting (2014 : Paris France_






International Society of Neurochemistry (ISN) and the European Society for Neurochemistry (ESN)


78 - 164


Wiley-Blackwell Publishing


Paris, France

Place of publication

Chichester, Eng.

Start date


End date








Publication classification

X Not reportable; E3 Extract of paper

Copyright notice

2017, The Authors

Title of proceedings

ISN - ESN 2017 : Proceedings of the joint meeting of the International Society of Neurochemistry (ISN) and the European Society for Neurochemistry (ESN)