Organoseleno cytostatic derivatives: autophagic cell death with AMPK and JNK activation

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dc.contributor.authorGarnica, Pablo
dc.contributor.authorEncío Martínez, Ignacio
dc.contributor.authorPlano, Daniel
dc.contributor.authorPalop, Juan Antonio
dc.contributor.authorSanmartín, Carmen
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2020-01-07T12:20:43Z
dc.date.available2021-08-01T23:00:12Z
dc.date.issued2019
dc.description.abstractSelenocyanates and diselenides are potential antitumor agents. Here we report two series of selenium derivatives related to selenocyanates and diselenides containing carboxylic, amide and imide moieties. These compounds were screened for their potency and selectivity against seven tumor cell lines and two non-malignant cell lines. Results showed that MCF-7 cells were especially sensitive to the treatment, with seven compounds presenting GI50 values below 10 μM. Notably, the carboxylic selenocyanate 8b and the cyclic imide 10a also displayed high selectivity for tumor cells. Treatment of MCF-7 cells with these compounds resulted in cell cycle arrest at S phase, increased levels of pJNK and pAMPK and caspase independent cell death. Autophagy inhibitors wortmannin and chloroquine partially prevented 8b and 10a induced cell death. Consistent with autophagy, increased Beclin1 and LC3-IIB and reduced SQSTM1/p62 levels were detected. Our results point to 8b and 10a as autophagic cell death inducers.en
dc.description.sponsorshipThe research leading to these results has received funding from 'La Caixa' Banking Foundation. P. Garnica wishes to express his gratitude to the Asociación de Amigos de la Universidad de Navarra for the pre-doctoral fellowship. Furthermore, the authors wish to express their gratitude to the Plan de Investigación de la Universidad de Navarra, PIUNA (Ref 2014–26 ) as well as Calgary Foundation for financial support for the project.en
dc.embargo.lift2021-08-01
dc.embargo.terms2021-08-01
dc.format.extent85 p.
dc.format.mimetypeapplication/pdfen
dc.identifier.doi10.1016/j.ejmech.2019.04.074
dc.identifier.issn0223-5234
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/36005
dc.language.isoengen
dc.publisherElsevier Masson SASen
dc.relation.ispartofEuropean Journal of Medicinal Chemistry 175 (2019) 234-246en
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//ECO2015-64330-P/ES/
dc.relation.publisherversionhttps://doi.org/10.1016/j.ejmech.2019.04.074
dc.rightsThis manuscript version is made available under the CC-BY-NC-ND 4.0.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAutophagyen
dc.subjectCanceren
dc.subjectCyclic imideen
dc.subjectDiselenideen
dc.subjectSelenocyanateen
dc.titleOrganoseleno cytostatic derivatives: autophagic cell death with AMPK and JNK activationen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication599ca381-1fd2-4a23-93ab-4373837eb6e0
relation.isAuthorOfPublication.latestForDiscovery599ca381-1fd2-4a23-93ab-4373837eb6e0

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