Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines

LAUR Repository

Show simple item record

dc.contributor.author Soukarieh, Rania
dc.date.accessioned 2022-06-16T06:50:38Z
dc.date.available 2022-06-16T06:50:38Z
dc.date.copyright 2021 en_US
dc.date.issued 2021-08-10
dc.identifier.uri http://hdl.handle.net/10725/13700
dc.description.abstract 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. en_US
dc.language.iso en en_US
dc.subject Bacillus anthracis -- Toxicology en_US
dc.subject Anthrax en_US
dc.subject Urokinase -- Therapeutic use en_US
dc.subject Cancer cells en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.title Effect of Anthrax Lethal Toxin on Activation of MAPK Pathway and Autophagy in AML Cell Lines en_US
dc.type Thesis en_US
dc.term.submitted Summer en_US
dc.author.degree Doctor of Pharmacy en_US
dc.author.school SAS en_US
dc.author.idnumber 201403804 en_US
dc.author.commembers Ghassibe-Sabbagh, Michella
dc.author.commembers Georgess, Dan
dc.author.department Natural Sciences en_US
dc.description.physdesc 1 online resource (xii, 52 leaves): ill. (some col.) en_US
dc.author.advisor Abi Habib, Ralph
dc.keywords AML en_US
dc.keywords Anthrax Lethal Toxin en_US
dc.keywords MAPK Pathway en_US
dc.keywords Autophagy en_US
dc.keywords MEK1/2 en_US
dc.keywords ERK1/2 en_US
dc.keywords LC3 en_US
dc.description.bibliographiccitations Includes bibliographical references (leaf 47-52) en_US
dc.identifier.doi https://doi.org/10.26756/th.2022.214
dc.author.email rania.soukarieh@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

Files in this item

This item appears in the following Collection(s)

Show simple item record

Search LAUR

Advanced Search


My Account