Characterizing the Effect of Arginine Deprivation on Autophagic Response in Breast Cancer cells

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dc.contributor.author Haidar, Fatemah
dc.date.accessioned 2022-06-14T06:30:16Z
dc.date.available 2022-06-14T06:30:16Z
dc.date.copyright 2021 en_US
dc.date.issued 2021-08-06
dc.identifier.uri http://hdl.handle.net/10725/13648
dc.description.abstract The metabolism of arginine, a semi-essential amino acid, is required for homeostasis and deregulated in various diseases. When deprived of arginine, several types of cancers can modulate arginine synthesis mediated by the enzyme ASS1 or employ broader response mechanisms such as autophagy. The co-regulation of arginine metabolism and autophagy in breast cancer is poorly understood. In this project, we first inspected ASS-1 expression in human breast cancer patients and found that it decreases progressively with tumorigenesis and metastasis. Residual ASS1 tumor expression corelated with increased metastasis and decreased survival in patient luminal A, Her2+ and triple-negative breast cancer. We then utilize a pharmacological-grade formulation of human recombinant arginase (HuArgI(Co)-PEG5000) to characterize the effect of arginine deprivation in one luminal (MCF-7) and two triple negative (MDA-MB-231 and UACC-2087) models of breast cancer. Western blot analysis revealed that arginine deprivation was not sufficient to trigger a compensatory upregulation of ASS1 expression in any of the tested cell lines. However, arginine deprivation induced varying autophagic response in MCF-7, MDA-MB-231 and UACC-2087. Altogether, our findings suggest that the activation of autophagy could be a plausible mechanism for breast cancer cells to overcome arginine depletion. Future functional studies will reveal whether HuArgI(Co)-PEG5000-induced autophagy sustains long-term cancer cell survival, and whether combination with autophagy inhibitors constitutes a viable therapeutic strategy in breast cancer. en_US
dc.language.iso en en_US
dc.subject Arginine -- Therapeutic use en_US
dc.subject Breast -- Cancer -- Prevention en_US
dc.subject Autophagic vacuoles -- Therapeutic use en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.title Characterizing the Effect of Arginine Deprivation on Autophagic Response in Breast Cancer cells 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 201905866 en_US
dc.author.commembers Ghassibe-Sabbagh, Michella
dc.author.commembers Abi-Habib, Ralph
dc.author.department Natural Sciences en_US
dc.description.physdesc 1 online resource (xii, 57 leaves) : col. ill. en_US
dc.author.advisor Georgess, Dan
dc.keywords Arginine en_US
dc.keywords Arginase en_US
dc.keywords Breast Cancer en_US
dc.keywords Autophagy en_US
dc.keywords ASS 1 en_US
dc.description.bibliographiccitations Includes bibliographical references (leaf 38-57.) en_US
dc.identifier.doi https://doi.org/10.26756/th.2022.263
dc.author.email fatemah.haidar@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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