Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent
In this study, we assess arginine auxotrophy in ovarian cancer cells and attempt to target them using arginine deprivation induced by a pegylated recombinant human Arginase I cobalt [HuArgI (Co)-PEG5000]. Ovarian cancer cells were sensitive to [HuArgI (Co)-PEG5000]-induced arginine deprivation with...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , |
| التنسيق: | article |
| منشور في: |
2019
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/11815 https://doi.org/10.1007/s10637-019-00756-w http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://link.springer.com/article/10.1007/s10637-019-00756-w |
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| _version_ | 1864513489324736512 |
|---|---|
| author | Nasreddine, Ghenwa |
| author2 | El-Sibai, Mirvat Abi-Habib, Ralph J. |
| author2_role | author author |
| author_facet | Nasreddine, Ghenwa El-Sibai, Mirvat Abi-Habib, Ralph J. |
| author_role | author |
| dc.creator.none.fl_str_mv | Nasreddine, Ghenwa El-Sibai, Mirvat Abi-Habib, Ralph J. |
| dc.date.none.fl_str_mv | 2019 2020-02-27T14:43:18Z 2020-02-27T14:43:18Z 2020-02-27 |
| dc.identifier.none.fl_str_mv | 1573-0646 http://hdl.handle.net/10725/11815 https://doi.org/10.1007/s10637-019-00756-w Nasreddine, G., El-Sibai, M., & Abi-Habib, R. J. (2020). Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent. Investigational new drugs, 38(1), 10-19. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://link.springer.com/article/10.1007/s10637-019-00756-w |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Investigational New Drugs |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | In this study, we assess arginine auxotrophy in ovarian cancer cells and attempt to target them using arginine deprivation induced by a pegylated recombinant human Arginase I cobalt [HuArgI (Co)-PEG5000]. Ovarian cancer cells were sensitive to [HuArgI (Co)-PEG5000]-induced arginine deprivation with IC50 values in the low pM range. Addition of excess L-citrulline rescued only one of three cell lines tested, indicating that the majority of cell lines are completely auxotrophic for arginine. The expression pattern of argininosuccinate synthetase (ASS1) confirmed the degree of auxotrophy of ovarian cancer cell lines with completely auxotrophic cells not expressing ASS1 and partially auxotrophic cells expressing the enzyme. Ovarian cancer cell lines were negative for annexinV staining while showing loss of membrane integrity and absence of caspase activation, indicating caspase-independent, non-apoptotic cell death. [HuArgI (Co)-PEG5000]-induced arginine deprivation led to extensive and prolonged activation of autophagy, which proved to be deleterious to cell survival since its inhibition led to a significant decrease in cytotoxicity. This indicates that the activation of autophagy following arginine-deprivation, rather than being protective, mediates cell cytotoxicity leading to death by autophagy. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_2ffedfe6806943d38eb66ba61ab2d520 |
| identifier_str_mv | 1573-0646 Nasreddine, G., El-Sibai, M., & Abi-Habib, R. J. (2020). Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent. Investigational new drugs, 38(1), 10-19. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/11815 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependentNasreddine, GhenwaEl-Sibai, MirvatAbi-Habib, Ralph J.In this study, we assess arginine auxotrophy in ovarian cancer cells and attempt to target them using arginine deprivation induced by a pegylated recombinant human Arginase I cobalt [HuArgI (Co)-PEG5000]. Ovarian cancer cells were sensitive to [HuArgI (Co)-PEG5000]-induced arginine deprivation with IC50 values in the low pM range. Addition of excess L-citrulline rescued only one of three cell lines tested, indicating that the majority of cell lines are completely auxotrophic for arginine. The expression pattern of argininosuccinate synthetase (ASS1) confirmed the degree of auxotrophy of ovarian cancer cell lines with completely auxotrophic cells not expressing ASS1 and partially auxotrophic cells expressing the enzyme. Ovarian cancer cell lines were negative for annexinV staining while showing loss of membrane integrity and absence of caspase activation, indicating caspase-independent, non-apoptotic cell death. [HuArgI (Co)-PEG5000]-induced arginine deprivation led to extensive and prolonged activation of autophagy, which proved to be deleterious to cell survival since its inhibition led to a significant decrease in cytotoxicity. This indicates that the activation of autophagy following arginine-deprivation, rather than being protective, mediates cell cytotoxicity leading to death by autophagy.PublishedN/A2020-02-27T14:43:18Z2020-02-27T14:43:18Z20192020-02-27Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1573-0646http://hdl.handle.net/10725/11815https://doi.org/10.1007/s10637-019-00756-wNasreddine, G., El-Sibai, M., & Abi-Habib, R. J. (2020). Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent. Investigational new drugs, 38(1), 10-19.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://link.springer.com/article/10.1007/s10637-019-00756-wenInvestigational New Drugsinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/118152021-03-19T10:47:39Z |
| spellingShingle | Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent Nasreddine, Ghenwa |
| status_str | publishedVersion |
| title | Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent |
| title_full | Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent |
| title_fullStr | Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent |
| title_full_unstemmed | Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent |
| title_short | Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent |
| title_sort | Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent |
| url | http://hdl.handle.net/10725/11815 https://doi.org/10.1007/s10637-019-00756-w http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://link.springer.com/article/10.1007/s10637-019-00756-w |