Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines
Anthrax lethal toxin is an A-B toxin consisting of protective antigen (PrAg), the cell binding and translocation domain, and lethal factor (LF), the catalytic domain, which cleaves all mitogen-activated protein/extracellular regulated kinase kinases (MEKs), leading to the inhibition of the MAPK path...
محفوظ في:
| المؤلف الرئيسي: | |
|---|---|
| التنسيق: | masterThesis |
| منشور في: |
2021
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| الموضوعات: | |
| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/13700 https://doi.org/10.26756/th.2022.214 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |
| الوسوم: |
إضافة وسم
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| _version_ | 1864513467982020608 |
|---|---|
| author | Soukarieh, Rania |
| author_facet | Soukarieh, Rania |
| author_role | author |
| dc.creator.none.fl_str_mv | Soukarieh, Rania |
| dc.date.none.fl_str_mv | 2021 2021-08-10 2022-06-16T06:50:38Z 2022-06-16T06:50:38Z |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10725/13700 https://doi.org/10.26756/th.2022.214 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 | Bacillus anthracis -- Toxicology Anthrax Urokinase -- Therapeutic use Cancer cells Lebanese American University -- Dissertations Dissertations, Academic |
| dc.title.none.fl_str_mv | Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines |
| dc.type.none.fl_str_mv | Thesis info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/masterThesis |
| description | Anthrax lethal toxin is an A-B toxin consisting of protective antigen (PrAg), the cell binding and translocation domain, and lethal factor (LF), the catalytic domain, which cleaves all mitogen-activated protein/extracellular regulated kinase kinases (MEKs), leading to the inhibition of the MAPK pathway. Anthrax lethal toxin has been extensively studied for its antitumor effect and showed potency against the majority of acute myeloid leukemia cell lines. In addition to that, previous data have shown that autophagy is activated in most AML cell lines. In this study we investigate the effect of anthrax lethal toxin on the downstream effectors of MEK in the Ras-Raf-MEK-ERK pathway, investigate the effect of MEK inhibition on the downregulation of ERK and try to explore the mechanism underlying autophagy which plays a protective role at later time points, as previously shown. This study aims to explain the difference in susceptibility of different AML cell lines. Flow cytometry analysis of downstream effectors of MEK showed decrease in phosphorylation of ERK and its downstream effectors only at early time points in sensitive cell lines. Whereas this pattern was not observed in resistant cell lines that showed a constant level of activation up to 120 hours after treatment. Finally, the effect on autophagy is to be more studied by testing for the expression of more proteins involved. |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| id | LAURepo_504869b85c5f8a365edea9dde1ea3840 |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/13700 |
| publishDate | 2021 |
| publisher.none.fl_str_mv | Lebanese American University |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell LinesSoukarieh, RaniaBacillus anthracis -- ToxicologyAnthraxUrokinase -- Therapeutic useCancer cellsLebanese American University -- DissertationsDissertations, AcademicAnthrax lethal toxin is an A-B toxin consisting of protective antigen (PrAg), the cell binding and translocation domain, and lethal factor (LF), the catalytic domain, which cleaves all mitogen-activated protein/extracellular regulated kinase kinases (MEKs), leading to the inhibition of the MAPK pathway. Anthrax lethal toxin has been extensively studied for its antitumor effect and showed potency against the majority of acute myeloid leukemia cell lines. In addition to that, previous data have shown that autophagy is activated in most AML cell lines. In this study we investigate the effect of anthrax lethal toxin on the downstream effectors of MEK in the Ras-Raf-MEK-ERK pathway, investigate the effect of MEK inhibition on the downregulation of ERK and try to explore the mechanism underlying autophagy which plays a protective role at later time points, as previously shown. This study aims to explain the difference in susceptibility of different AML cell lines. Flow cytometry analysis of downstream effectors of MEK showed decrease in phosphorylation of ERK and its downstream effectors only at early time points in sensitive cell lines. Whereas this pattern was not observed in resistant cell lines that showed a constant level of activation up to 120 hours after treatment. Finally, the effect on autophagy is to be more studied by testing for the expression of more proteins involved.1 online resource (xii, 52 leaves): ill. (some col.)Includes bibliographical references (leaf 47-52)Lebanese American University2022-06-16T06:50:38Z2022-06-16T06:50:38Z20212021-08-10Thesisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttp://hdl.handle.net/10725/13700https://doi.org/10.26756/th.2022.214http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.phpeninfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/137002024-02-15T12:12:01Z |
| spellingShingle | Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines Soukarieh, Rania Bacillus anthracis -- Toxicology Anthrax Urokinase -- Therapeutic use Cancer cells Lebanese American University -- Dissertations Dissertations, Academic |
| status_str | publishedVersion |
| title | Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines |
| title_full | Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines |
| title_fullStr | Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines |
| title_full_unstemmed | Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines |
| title_short | Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines |
| title_sort | Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines |
| topic | Bacillus anthracis -- Toxicology Anthrax Urokinase -- Therapeutic use Cancer cells Lebanese American University -- Dissertations Dissertations, Academic |
| url | http://hdl.handle.net/10725/13700 https://doi.org/10.26756/th.2022.214 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |