Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin
Recent studies have investigated the use of retinoic acid (RA) molecule in combined chemotherapies to cancer cells as an attempt to increase treatment efficiency and circumvent cell resistance. Positive results were obtained in clinical trials from lung cancer patients treated with RA and cisplatin....
- Autores:
-
Gasparotto, Juciano
Figueiró, Fabrício
de Fraga Dias, Amanda
Rostirolla, Diana Carolina
Somensi, Nauana
Taisda Rosa, Helen
Kich Grun, Lucas
Barbé Tuana, Florencia María
- Tipo de recurso:
- http://purl.org/coar/resource_type/c_816b
- Fecha de publicación:
- 2019
- Institución:
- Corporación Universidad de la Costa
- Repositorio:
- REDICUC - Repositorio CUC
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.cuc.edu.co:11323/5233
- Acceso en línea:
- http://hdl.handle.net/11323/5233
https://repositorio.cuc.edu.co/
- Palabra clave:
- Retinoic acid
Cisplatin
A549 cells
NRF2
Antioxidants systems
Homologous recombination
- Rights
- openAccess
- License
- CC0 1.0 Universal
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oai_identifier_str |
oai:repositorio.cuc.edu.co:11323/5233 |
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RCUC2 |
network_name_str |
REDICUC - Repositorio CUC |
repository_id_str |
|
dc.title.spa.fl_str_mv |
Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin |
title |
Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin |
spellingShingle |
Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin Retinoic acid Cisplatin A549 cells NRF2 Antioxidants systems Homologous recombination |
title_short |
Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin |
title_full |
Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin |
title_fullStr |
Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin |
title_full_unstemmed |
Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin |
title_sort |
Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin |
dc.creator.fl_str_mv |
Gasparotto, Juciano Figueiró, Fabrício de Fraga Dias, Amanda Rostirolla, Diana Carolina Somensi, Nauana Taisda Rosa, Helen Kich Grun, Lucas Barbé Tuana, Florencia María |
dc.contributor.author.spa.fl_str_mv |
Gasparotto, Juciano Figueiró, Fabrício de Fraga Dias, Amanda Rostirolla, Diana Carolina Somensi, Nauana Taisda Rosa, Helen Kich Grun, Lucas Barbé Tuana, Florencia María |
dc.subject.spa.fl_str_mv |
Retinoic acid Cisplatin A549 cells NRF2 Antioxidants systems Homologous recombination |
topic |
Retinoic acid Cisplatin A549 cells NRF2 Antioxidants systems Homologous recombination |
description |
Recent studies have investigated the use of retinoic acid (RA) molecule in combined chemotherapies to cancer cells as an attempt to increase treatment efficiency and circumvent cell resistance. Positive results were obtained in clinical trials from lung cancer patients treated with RA and cisplatin. Meanwhile, the signalling process that results from the interaction of both molecules remains unclear. One of the pathways that RA is able to modulate is the activity of NRF2 transcription factor, which is highly associated with tumour progression and resistance. Therefore, the aim of this work was to investigate molecular mechanism of RA and cisplatin co-treatment in A549 cells, focusing in NRF2 pathway. To this end, we investigated NRF2 and NRF2-target genes expression, cellular redox status, cisplatin-induced apoptosis, autophagy and DNA repair through homologous recombination. RA demonstrated to have an inhibitory effect over NRF2 activation, which regulates the expression of thiol antioxidants enzymes. Moreover, RA increased reactive species production associated with increased oxidation of thiol groups within the cells. The expression of proteins associated with DNA repair through homologous recombination was also suppressed by RA pre-treatment. All combined, these effects appear to create a more sensitive cellular environment to cisplatin treatment, increasing apoptosis frequency. Interestingly, autophagy was also increased by combination therapy, suggesting a resistance mechanism by A549 cells. In conclusion, these results provided new information about molecular mechanisms of RA and cisplatin treatment contributing to chemotherapy optimization. |
publishDate |
2019 |
dc.date.accessioned.none.fl_str_mv |
2019-09-03T14:50:11Z |
dc.date.available.none.fl_str_mv |
2019-09-03T14:50:11Z |
dc.date.issued.none.fl_str_mv |
2019-10 |
dc.type.spa.fl_str_mv |
Pre-Publicación |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_816b |
dc.type.content.spa.fl_str_mv |
Text |
dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/preprint |
dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/ARTOTR |
dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
format |
http://purl.org/coar/resource_type/c_816b |
status_str |
acceptedVersion |
dc.identifier.uri.spa.fl_str_mv |
http://hdl.handle.net/11323/5233 |
dc.identifier.instname.spa.fl_str_mv |
Corporación Universidad de la Costa |
dc.identifier.reponame.spa.fl_str_mv |
REDICUC - Repositorio CUC |
dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.cuc.edu.co/ |
url |
http://hdl.handle.net/11323/5233 https://repositorio.cuc.edu.co/ |
identifier_str_mv |
Corporación Universidad de la Costa REDICUC - Repositorio CUC |
dc.language.iso.none.fl_str_mv |
eng |
language |
eng |
dc.rights.spa.fl_str_mv |
CC0 1.0 Universal |
dc.rights.uri.spa.fl_str_mv |
http://creativecommons.org/publicdomain/zero/1.0/ |
dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
dc.rights.coar.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
rights_invalid_str_mv |
CC0 1.0 Universal http://creativecommons.org/publicdomain/zero/1.0/ http://purl.org/coar/access_right/c_abf2 |
eu_rights_str_mv |
openAccess |
dc.publisher.spa.fl_str_mv |
Universidad de la Costa |
institution |
Corporación Universidad de la Costa |
bitstream.url.fl_str_mv |
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Gasparotto, Jucianoe516b1d6b3d6b85ef4941a6ac7ad8fa0Figueiró, Fabrício72635797efa1b93051e0a27e12ee87c7de Fraga Dias, Amandacdc953dbd418e08b01f5d14bc25f6be4Rostirolla, Diana Carolina5ebfe0310d8473bf81f544b9eb8df204Somensi, Nauana6862d84b6225d942279a368819d369eaTaisda Rosa, Helenfa7007173e58e41327ae2dc5b3177cebKich Grun, Lucasbe1a376c9fefc2517d5f5311a7397eb9Barbé Tuana, Florencia Maríafbb8df8446877c00c49a7c4d125a1b612019-09-03T14:50:11Z2019-09-03T14:50:11Z2019-10http://hdl.handle.net/11323/5233Corporación Universidad de la CostaREDICUC - Repositorio CUChttps://repositorio.cuc.edu.co/Recent studies have investigated the use of retinoic acid (RA) molecule in combined chemotherapies to cancer cells as an attempt to increase treatment efficiency and circumvent cell resistance. Positive results were obtained in clinical trials from lung cancer patients treated with RA and cisplatin. Meanwhile, the signalling process that results from the interaction of both molecules remains unclear. One of the pathways that RA is able to modulate is the activity of NRF2 transcription factor, which is highly associated with tumour progression and resistance. Therefore, the aim of this work was to investigate molecular mechanism of RA and cisplatin co-treatment in A549 cells, focusing in NRF2 pathway. To this end, we investigated NRF2 and NRF2-target genes expression, cellular redox status, cisplatin-induced apoptosis, autophagy and DNA repair through homologous recombination. RA demonstrated to have an inhibitory effect over NRF2 activation, which regulates the expression of thiol antioxidants enzymes. Moreover, RA increased reactive species production associated with increased oxidation of thiol groups within the cells. The expression of proteins associated with DNA repair through homologous recombination was also suppressed by RA pre-treatment. All combined, these effects appear to create a more sensitive cellular environment to cisplatin treatment, increasing apoptosis frequency. Interestingly, autophagy was also increased by combination therapy, suggesting a resistance mechanism by A549 cells. In conclusion, these results provided new information about molecular mechanisms of RA and cisplatin treatment contributing to chemotherapy optimization.engUniversidad de la CostaCC0 1.0 Universalhttp://creativecommons.org/publicdomain/zero/1.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Retinoic acidCisplatinA549 cellsNRF2Antioxidants systemsHomologous recombinationRetinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatinPre-Publicaciónhttp://purl.org/coar/resource_type/c_816bTextinfo:eu-repo/semantics/preprinthttp://purl.org/redcol/resource_type/ARTOTRinfo:eu-repo/semantics/acceptedVersionORIGINALRetinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin.pdfRetinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin.pdfapplication/pdf63831https://repositorio.cuc.edu.co/bitstream/11323/5233/1/Retinoic%20acid%20downregulates%20thiol%20antioxidant%20defences%20and%20homologous%20recombination%20while%20promotes%20A549%20cells%20sensitization%20to%20cisplatin.pdfe74d3ae71ec90a469f3b9f08719c7a88MD51open accessCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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