A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells
Symmetric aromatic diselenides are potential anticancer agents with strong cytotoxic activity. In this study, the in vitro anticancer activities of a novel series of diarylseleno derivatives from the diphenyldiselenide (DPDS) scaffold were evaluated. Most of the compounds exhibited high efficacy for...
| Autores: | , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/64738 |
| Acceso en línea: | https://hdl.handle.net/10171/64738 |
| Access Level: | acceso abierto |
| Palabra clave: | p53 p38 MAPK JNK Diphenyldiselenide Autophagy |
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A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cellsDiaz, M. (Marta)|||/items/cde81b70-e69d-433e-aabc-cf4dbecff8baGonzález, R. (Roncesvalles)|||/items/0fd6fddd-3be4-4b17-9ecd-5c0d1f7811d9Plano-Amatriain, D. (Daniel)|||/items/238881e4-7d5e-4598-924d-4392e3b7e02ePalop-Cubillo, J.A. (Juan Antonio)|||/items/bfa23090-c589-4aeb-89e5-bbe9aa243a90Sanmartin-Grijalba, C. (Carmen)|||/items/d36bd105-ab64-427d-9745-5812cf5e7af7Encío-Martínez, I.J. (Ignacio José)|||/items/468e76be-1795-41af-a6a3-f7c4472e416cp53p38 MAPKJNKDiphenyldiselenideAutophagySymmetric aromatic diselenides are potential anticancer agents with strong cytotoxic activity. In this study, the in vitro anticancer activities of a novel series of diarylseleno derivatives from the diphenyldiselenide (DPDS) scaffold were evaluated. Most of the compounds exhibited high efficacy for inducing cytotoxicity against different human cancer cell lines. DPDS 2, the compound with the lowest mean GI50 value, induced both caspase-dependent apoptosis and arrest at the G0/G1 phase in acute lymphoblastic leucemia CCRF-CEM cells. Consistent with this, PARP cleavage; enhanced caspase-2, -3, -8 and -9 activity; reduced CDK4 expression and increased levels of p53 were detected in these cells upon DPDS 2 treatment. Mutated p53 expressed in CCRF-CEM cells retains its transactivating activity. Therefore, increased levels of p21CIP1 and BAX proteins were also detected. On the other hand, DPDS 6, the compound with the highest selectivity index for cancer cells, resulted in G2/M cell cycle arrest and caspase-independent cell death in p53 deficient HTB-54 lung cancer cells. Autophagy inhibitors 3-methyladenine, wortmannin and chloroquine inhibited DPDS 6-induced cell death. Consistent with autophagy, increased LC3-II and decreased SQSTM1/p62 levels were detected in HTB-54 cells in response to DPDS 6. Induction of JNK phosphorylation and a reduction in phospho-p38 MAPK were also detected. Moreover, the JNK inhibitor SP600125-protected HTB-54 cells from DPDS 6-induced cell death indicating that JNK activation is involved in DPDS 6-induced autophagy. These results highlight the anticancer effects of these derivatives and warrant future studies examining their clinical potential.WileyDadun. Depósito Académico Digital Universidad de Navarra20222022-11-3020182018-01-0120182018-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/64738reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/647382026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells |
| title |
A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells |
| spellingShingle |
A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells Diaz, M. (Marta)|||/items/cde81b70-e69d-433e-aabc-cf4dbecff8ba p53 p38 MAPK JNK Diphenyldiselenide Autophagy |
| title_short |
A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells |
| title_full |
A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells |
| title_fullStr |
A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells |
| title_full_unstemmed |
A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells |
| title_sort |
A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells |
| dc.creator.none.fl_str_mv |
Diaz, M. (Marta)|||/items/cde81b70-e69d-433e-aabc-cf4dbecff8ba González, R. (Roncesvalles)|||/items/0fd6fddd-3be4-4b17-9ecd-5c0d1f7811d9 Plano-Amatriain, D. (Daniel)|||/items/238881e4-7d5e-4598-924d-4392e3b7e02e Palop-Cubillo, J.A. (Juan Antonio)|||/items/bfa23090-c589-4aeb-89e5-bbe9aa243a90 Sanmartin-Grijalba, C. (Carmen)|||/items/d36bd105-ab64-427d-9745-5812cf5e7af7 Encío-Martínez, I.J. (Ignacio José)|||/items/468e76be-1795-41af-a6a3-f7c4472e416c |
| author |
Diaz, M. (Marta)|||/items/cde81b70-e69d-433e-aabc-cf4dbecff8ba |
| author_facet |
Diaz, M. (Marta)|||/items/cde81b70-e69d-433e-aabc-cf4dbecff8ba González, R. (Roncesvalles)|||/items/0fd6fddd-3be4-4b17-9ecd-5c0d1f7811d9 Plano-Amatriain, D. (Daniel)|||/items/238881e4-7d5e-4598-924d-4392e3b7e02e Palop-Cubillo, J.A. (Juan Antonio)|||/items/bfa23090-c589-4aeb-89e5-bbe9aa243a90 Sanmartin-Grijalba, C. (Carmen)|||/items/d36bd105-ab64-427d-9745-5812cf5e7af7 Encío-Martínez, I.J. (Ignacio José)|||/items/468e76be-1795-41af-a6a3-f7c4472e416c |
| author_role |
author |
| author2 |
González, R. (Roncesvalles)|||/items/0fd6fddd-3be4-4b17-9ecd-5c0d1f7811d9 Plano-Amatriain, D. (Daniel)|||/items/238881e4-7d5e-4598-924d-4392e3b7e02e Palop-Cubillo, J.A. (Juan Antonio)|||/items/bfa23090-c589-4aeb-89e5-bbe9aa243a90 Sanmartin-Grijalba, C. (Carmen)|||/items/d36bd105-ab64-427d-9745-5812cf5e7af7 Encío-Martínez, I.J. (Ignacio José)|||/items/468e76be-1795-41af-a6a3-f7c4472e416c |
| author2_role |
author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
p53 p38 MAPK JNK Diphenyldiselenide Autophagy |
| topic |
p53 p38 MAPK JNK Diphenyldiselenide Autophagy |
| description |
Symmetric aromatic diselenides are potential anticancer agents with strong cytotoxic activity. In this study, the in vitro anticancer activities of a novel series of diarylseleno derivatives from the diphenyldiselenide (DPDS) scaffold were evaluated. Most of the compounds exhibited high efficacy for inducing cytotoxicity against different human cancer cell lines. DPDS 2, the compound with the lowest mean GI50 value, induced both caspase-dependent apoptosis and arrest at the G0/G1 phase in acute lymphoblastic leucemia CCRF-CEM cells. Consistent with this, PARP cleavage; enhanced caspase-2, -3, -8 and -9 activity; reduced CDK4 expression and increased levels of p53 were detected in these cells upon DPDS 2 treatment. Mutated p53 expressed in CCRF-CEM cells retains its transactivating activity. Therefore, increased levels of p21CIP1 and BAX proteins were also detected. On the other hand, DPDS 6, the compound with the highest selectivity index for cancer cells, resulted in G2/M cell cycle arrest and caspase-independent cell death in p53 deficient HTB-54 lung cancer cells. Autophagy inhibitors 3-methyladenine, wortmannin and chloroquine inhibited DPDS 6-induced cell death. Consistent with autophagy, increased LC3-II and decreased SQSTM1/p62 levels were detected in HTB-54 cells in response to DPDS 6. Induction of JNK phosphorylation and a reduction in phospho-p38 MAPK were also detected. Moreover, the JNK inhibitor SP600125-protected HTB-54 cells from DPDS 6-induced cell death indicating that JNK activation is involved in DPDS 6-induced autophagy. These results highlight the anticancer effects of these derivatives and warrant future studies examining their clinical potential. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2018-01-01 2018 2018-01-01 2022 2022-11-30 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/64738 |
| url |
https://hdl.handle.net/10171/64738 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley |
| publisher.none.fl_str_mv |
Wiley |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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15.300719 |