Potential mechanisms of human recombinant arginase I (Co)-PEG5000 [HuArgI (CO) - PRG5000] induced cytotoxicity in glioblastoma cells. (c2018)

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dc.contributor.author El Jawhari, Yassmine
dc.date.accessioned 2018-10-17T07:01:54Z
dc.date.available 2018-10-17T07:01:54Z
dc.date.copyright 2018 en_US
dc.date.issued 2018-10-17
dc.date.submitted 2018-06-23
dc.identifier.uri http://hdl.handle.net/10725/8650
dc.description.abstract Glioblastoma multiforme (GBM) is a highly aggressive glioma arising in the central nervous system accounting for more than 70% of all brain tumors. Due to the resistance and complexity of the tumor itself, it is characterized by a low survival rate and decreased prognosis. Therefore, more selective and efficient therapeutic methods for targeting GBM are needed. In this study, we attempted to investigate the potency of arginine depletion to target GBM cells through the use of human recombinant Arginase I cobalt [HuArgI(Co)] coupled with polyethylene glycol 5000 [HuArgI (Co)-PEG5000]. Cytotoxicity of [HuArgI (Co)-PEG5000] was tested on two GBM cell lines, namely A172 and U251. Both cell lines showed increased sensitivity at longer incubation periods of [HuArgI (Co)-PEG5000] treatment with IC50 values in the pM range, a result attributable to the arginine auxotrophy expressed in those two cell lines. The addition of chloroquine, an autophagy inhibitor, increased the sensitivity of cells to [HuArgI (Co)-PEG5000]-mediated arginine depletion at earlier time points. We also concluded that autophagy was activated in response to arginine depletion and plays a protective role at early time points. However, the excessive accumulation of intracellular autophagosomes upon treatment with chloroquine at later time points illustrates the role of autophagy in response to [HuArgI (Co)-PEG5000]-mediated arginine depletion resulting in ultimate cell death by autophagy. Overall, in this study we showed how arginine auxotrophy in GBM could be used to target such cells through HuArgI (Co)-PEG5000. Hence, HuArgI (Co)-PEG5000 is an efficient and selective therapeutic method for targeting GBM. en_US
dc.language.iso en en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.subject Glioblastoma multiforme en_US
dc.subject Arginine -- Therapeutic use en_US
dc.title Potential mechanisms of human recombinant arginase I (Co)-PEG5000 [HuArgI (CO) - PRG5000] induced cytotoxicity in glioblastoma cells. (c2018) en_US
dc.type Thesis en_US
dc.term.submitted Summer en_US
dc.author.degree MS in Molecular Biology en_US
dc.author.school SAS en_US
dc.author.idnumber 201206169 en_US
dc.author.commembers Khalaf, Roy
dc.author.commembers Tokajian, Sima
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.description.physdesc 1 hard copy: xii, 47 leaves; 30 cm. available at RNL. en_US
dc.author.advisor Abi-Habib, Ralph
dc.keywords Glioblastoma multiforme en_US
dc.keywords Cytotoxicity en_US
dc.keywords Autophagy en_US
dc.keywords Arginine Deprivation en_US
dc.keywords HuArgI (Co)-PEG5000 en_US
dc.keywords Arginine Auxotrophy en_US
dc.description.bibliographiccitations Bibliography : leaves 38-47. en_US
dc.identifier.doi https://doi.org/10.26756/th.2018.101 en_US
dc.author.email yassmine.eljawhari@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php en_US
dc.publisher.institution Lebanese American University en_US
dc.author.affiliation Lebanese American University en_US

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