Organoseleno cytostatic derivatives: autophagic cell death with AMPK and JNK activation
Fecha
2019Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión aceptada / Onetsi den bertsioa
Impacto
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10.1016/j.ejmech.2019.04.074
Resumen
Selenocyanates 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 t ...
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Selenocyanates 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. [--]
Materias
Autophagy,
Cancer,
Cyclic imide,
Diselenide,
Selenocyanate
Editor
Elsevier Masson SAS
Publicado en
European Journal of Medicinal Chemistry 175 (2019) 234-246
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
The 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.