Mechanisms Of Cell Death Induced by Arginine Depletion Using Human Recombinant Arginase I (Co)-PEG5000 in Glioblastoma Cells (GBM)
Glioblastoma Multiforme (GBM), constituting a predominant subtype of malignant brain cancers, presents a crucial challenge due to poor prognosis, the blood-brain barrier,intra-tumoral heterogeneity , and glioblastoma stem cells, hindering efficient therapeutic strategies. This study employs human re...
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| Format: | masterThesis |
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2023
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| Online Access: | http://hdl.handle.net/10725/15806 https://doi.org/10.26756/th.2023.665 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |
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| _version_ | 1864513471753748480 |
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| author | Shaheen, Maha |
| author_facet | Shaheen, Maha |
| author_role | author |
| dc.creator.none.fl_str_mv | Shaheen, Maha |
| dc.date.none.fl_str_mv | 2023 2023-12-19 2024-06-27T07:12:57Z 2024-06-27T07:12:57Z |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10725/15806 https://doi.org/10.26756/th.2023.665 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |
| dc.language.none.fl_str_mv | en |
| dc.publisher.none.fl_str_mv | Lebanese American University |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Lebanese American University--Dissertations Dissertations, Academic Glioblastoma multiforme Brain--Cancer Cell death Apoptosis |
| dc.title.none.fl_str_mv | Mechanisms Of Cell Death Induced by Arginine Depletion Using Human Recombinant Arginase I (Co)-PEG5000 in Glioblastoma Cells (GBM) |
| dc.type.none.fl_str_mv | Thesis info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/masterThesis |
| description | Glioblastoma Multiforme (GBM), constituting a predominant subtype of malignant brain cancers, presents a crucial challenge due to poor prognosis, the blood-brain barrier,intra-tumoral heterogeneity , and glioblastoma stem cells, hindering efficient therapeutic strategies. This study employs human recombinant arginase ([HuArgI(Co)-PEG5000]) as a targeted therapeutic agent to induce arginine deprivation in fully and partially auxotrophic GBM cells. The objective is to investigate the mechanism of arginine deprivation involved in arginine deprivation induced-cell death in GBM cells, and to investigative the potential link to ferroptosis. Our results reveal that [HuArgI(Co)-PEG5000] activated autophagy and induces cytotoxicity in GBM, leading to ROS accumulation. This was mitigated through the use ROS scavenging agents N-acetyl-l-cysteine (NAC). Examination of key regulatory proteins involved in iron homeostasis (NCOA4 and FTH1) and oxidative stress defenses (and GPX4) suggests altered iron distribution impairing the antioxidant system in treated cells. This indicates that ferroptosis is downstream of autophagy mediated cell death. In summary, our results emphasize that the depletion of arginine through [HuArgI(Co)-PEG5000] treatment triggers elevated production of ROS, lipid peroxidation, and perturbation of iron metabolism and antioxidant pathways, this suggests that arginine deprivation induced by [HuArgI(Co)- PEG5000] in GBM causes death by ferroptosis, an autophagy-mediated cell death. Understanding these mechanisms holds implications for developing targeted therapies not only for GBM but also for other cancer types. |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| id | LAURepo_853f3aebdbd9f6571706c66d64352727 |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/15806 |
| publishDate | 2023 |
| publisher.none.fl_str_mv | Lebanese American University |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Mechanisms Of Cell Death Induced by Arginine Depletion Using Human Recombinant Arginase I (Co)-PEG5000 in Glioblastoma Cells (GBM)Shaheen, MahaLebanese American University--DissertationsDissertations, AcademicGlioblastoma multiformeBrain--CancerCell deathApoptosisGlioblastoma Multiforme (GBM), constituting a predominant subtype of malignant brain cancers, presents a crucial challenge due to poor prognosis, the blood-brain barrier,intra-tumoral heterogeneity , and glioblastoma stem cells, hindering efficient therapeutic strategies. This study employs human recombinant arginase ([HuArgI(Co)-PEG5000]) as a targeted therapeutic agent to induce arginine deprivation in fully and partially auxotrophic GBM cells. The objective is to investigate the mechanism of arginine deprivation involved in arginine deprivation induced-cell death in GBM cells, and to investigative the potential link to ferroptosis. Our results reveal that [HuArgI(Co)-PEG5000] activated autophagy and induces cytotoxicity in GBM, leading to ROS accumulation. This was mitigated through the use ROS scavenging agents N-acetyl-l-cysteine (NAC). Examination of key regulatory proteins involved in iron homeostasis (NCOA4 and FTH1) and oxidative stress defenses (and GPX4) suggests altered iron distribution impairing the antioxidant system in treated cells. This indicates that ferroptosis is downstream of autophagy mediated cell death. In summary, our results emphasize that the depletion of arginine through [HuArgI(Co)-PEG5000] treatment triggers elevated production of ROS, lipid peroxidation, and perturbation of iron metabolism and antioxidant pathways, this suggests that arginine deprivation induced by [HuArgI(Co)- PEG5000] in GBM causes death by ferroptosis, an autophagy-mediated cell death. Understanding these mechanisms holds implications for developing targeted therapies not only for GBM but also for other cancer types.1 online resource (xii, 84 leaves) : ill. (chiefly col.)Includes bibliographical references (leaves 78-84).Lebanese American University2024-06-27T07:12:57Z2024-06-27T07:12:57Z20232023-12-19Thesisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttp://hdl.handle.net/10725/15806https://doi.org/10.26756/th.2023.665http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.phpeninfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/158062024-06-27T07:12:57Z |
| spellingShingle | Mechanisms Of Cell Death Induced by Arginine Depletion Using Human Recombinant Arginase I (Co)-PEG5000 in Glioblastoma Cells (GBM) Shaheen, Maha Lebanese American University--Dissertations Dissertations, Academic Glioblastoma multiforme Brain--Cancer Cell death Apoptosis |
| status_str | publishedVersion |
| title | Mechanisms Of Cell Death Induced by Arginine Depletion Using Human Recombinant Arginase I (Co)-PEG5000 in Glioblastoma Cells (GBM) |
| title_full | Mechanisms Of Cell Death Induced by Arginine Depletion Using Human Recombinant Arginase I (Co)-PEG5000 in Glioblastoma Cells (GBM) |
| title_fullStr | Mechanisms Of Cell Death Induced by Arginine Depletion Using Human Recombinant Arginase I (Co)-PEG5000 in Glioblastoma Cells (GBM) |
| title_full_unstemmed | Mechanisms Of Cell Death Induced by Arginine Depletion Using Human Recombinant Arginase I (Co)-PEG5000 in Glioblastoma Cells (GBM) |
| title_short | Mechanisms Of Cell Death Induced by Arginine Depletion Using Human Recombinant Arginase I (Co)-PEG5000 in Glioblastoma Cells (GBM) |
| title_sort | Mechanisms Of Cell Death Induced by Arginine Depletion Using Human Recombinant Arginase I (Co)-PEG5000 in Glioblastoma Cells (GBM) |
| topic | Lebanese American University--Dissertations Dissertations, Academic Glioblastoma multiforme Brain--Cancer Cell death Apoptosis |
| url | http://hdl.handle.net/10725/15806 https://doi.org/10.26756/th.2023.665 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |