dc.contributor.author |
Khoury, Oula |
|
dc.contributor.author |
Ghazale, Noura |
|
dc.contributor.author |
Stone, Everett |
|
dc.contributor.author |
El-Sibai, Mirvat |
|
dc.contributor.author |
Frankel, Arthur |
|
dc.contributor.author |
Abi-Habib, Ralph J. |
|
dc.date.accessioned |
2015-12-01T07:41:40Z |
|
dc.date.available |
2015-12-01T07:41:40Z |
|
dc.date.copyright |
2015 |
|
dc.date.issued |
2015-12-01 |
|
dc.identifier.issn |
0167-594X |
en_US |
dc.identifier.uri |
http://hdl.handle.net/10725/2739 |
|
dc.description.abstract |
In this study, we attempt to target Arginine auxotrophy in glioblastoma multiforme (GBM) cells using a pegylated recombinant human Arginase I cobalt [HuArgI (Co)-PEG5000]. We tested and characterized the activity of HuArgI (Co)-PEG5000 on a panel of 9 GBM cell lines and on human fetal glial cells (SVG-p12). HuArgI (Co)-PEG5000 was cytotoxic to all GBM cells tested. SVG-p12 cells were not sensitive demonstrating the selective cytotoxicity of HuArgI (Co)-PEG5000-induced arginine deprivation. Addition of l-citrulline led to the rescue of 6 GBM cell lines but only at concentrations of 11.4 mM, reflecting the extent of arginine auxotrophy in GBM. The ability of l-citrulline to rescue cells was dependent on the expression of argininosuccinate synthetase-1 (ASS1) with the cells that were not rescued by l-citrulline being negative for ASS1 expression. Knocking-down ASS1 reversed the ability of l-citrulline to rescue GBM cells, further illustrating the dependence of arginine auxotrophy on ASS1 expression. Inhibition of autophagy increased cell sensitivity to HuArgI (Co)-PEG5000 indicating that, following arginine deprivation, autophagy plays a protective role in GBM cells. Analysis of the type of cell death revealed a lack of AnnexinV staining and caspase activation in HuArgI (Co)-PEG5000-treated cells, indicating that arginine deprivation induces caspase-independent, non-apoptotic cell death in GBM. We have shown that GBM cells are auxotrophic for arginine and can be selectively targeted using HuArgI (Co)-PEG5000-induced arginine depletion, thus demonstrating that l-Arginine deprivation is a potent and selective potential treatment for GBM. |
en_US |
dc.language.iso |
en |
en_US |
dc.title |
Human recombinant arginase I (Co)-PEG5000 [HuArgI (Co)-PEG5000]-induced arginine depletion is selectively cytotoxic to human glioblastoma cells |
en_US |
dc.type |
Article |
en_US |
dc.description.version |
Published |
en_US |
dc.author.school |
SAS |
en_US |
dc.author.idnumber |
200703859 |
en_US |
dc.author.idnumber |
200901419 |
en_US |
dc.author.woa |
N/A |
en_US |
dc.author.department |
Natural Sciences |
en_US |
dc.description.embargo |
N/A |
en_US |
dc.relation.journal |
Journal of Neuro-Oncology |
en_US |
dc.journal.volume |
122 |
en_US |
dc.journal.issue |
1 |
en_US |
dc.article.pages |
75-85 |
en_US |
dc.keywords |
HuArgI (Co)-PEG5000 |
en_US |
dc.keywords |
GBM |
en_US |
dc.keywords |
Arginine |
en_US |
dc.keywords |
Autophagy |
en_US |
dc.identifier.doi |
http://dx.doi.org/10.1007/s11060-014-1698-5 |
en_US |
dc.identifier.ctation |
Khoury, O., Ghazale, N., Stone, E., El-Sibai, M., Frankel, A. E., & Abi-Habib, R. J. (2015). Human recombinant arginase I (Co)-PEG5000 [HuArgI (Co)-PEG5000]-induced arginine depletion is selectively cytotoxic to human glioblastoma cells. Journal of neuro-oncology, 122(1), 75-85. |
en_US |
dc.author.email |
mirvat.elsibai@lau.edu.lb |
|
dc.author.email |
ralph.abihabib@lau.edu.lb |
|
dc.identifier.url |
http://link.springer.com/article/10.1007/s11060-014-1698-5 |
|
dc.orcid.id |
https://orcid.org/0000-0003-4084-6759 |
en_US |