Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer

Ovarian cancer is the most fatal of all the reproductive cancers within the female population, mainly due to its late diagnosis that limits surgery and medical treatment. Classically, ovarian cancer therapy has included conventional chemotherapy, and other therapeutic approaches are now being used t...

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Detalhes bibliográficos
Autores: Almaraz Postigo, Sheila, Sanz, Eduardo, Pandiella, Atanasio, Díaz-Rodríguez, Elena
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/381449
Acesso em linha:http://hdl.handle.net/10261/381449
Access Level:acceso abierto
Palavra-chave:Ovarian cancer
OOS
Antioxidants
DNA damage
Cell death
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spelling Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian CancerAlmaraz Postigo, SheilaSanz, EduardoPandiella, AtanasioDíaz-Rodríguez, ElenaOvarian cancerOOSAntioxidantsDNA damageCell deathOvarian cancer is the most fatal of all the reproductive cancers within the female population, mainly due to its late diagnosis that limits surgery and medical treatment. Classically, ovarian cancer therapy has included conventional chemotherapy, and other therapeutic approaches are now being used to treat these patients, but the outcomes of the disease are still poor. Therefore, new strategies are needed to improve life expectancy and life quality of ovarian cancer patients. Considering that, we investigated the effect of the nutritional supplement Ocoxin Oral Solution (OOS) in ovarian cancer models. OOS contains several nutritional supplements, some of them with demonstrated antitumoral action. In vitro studies showed that OOS inhibited the proliferation of several ovarian cancer cell lines, especially of those representative of the endometrioid subtype, in a time- and dose-dependent manner. A fast cell death induction after OOS treatment was observed, and when the molecular mechanisms leading to this effect were investigated, an activation of the DNA damage checkpoint was detected, as shown by activation (phosphorylation) of CHK1 and CHK2 kinases that was followed by the phosphorylation of the target protein histone H2AX. When tested in animal models of ovarian cancer, OOS reduced tumor growth without any observed secondary effects. Moreover, such reduction in tumor proliferation was caused by the induction of DNA damage as corroborated by the in vivo phosphorylation of CHK2 and Histone H2AX. Finally, OOS potentiated the action of carboplatin or olaparib, the standard of care treatments used in ovarian clinics, opening the possibility of including OOS in combination with those standard of care agents in patients with ovarian cancer.This work was partially supported by the Ministry of Economy and Competitiveness of Spain (BFU2015-71371-R and PID2020-115605RB-I00), the Instituto de Salud Carlos III through CIBERONC (CB16/12/00317), Junta de Castilla y León (CSI146P20), ALMOM, ACMUMA, UCCTA, the CRIS Cancer Foundation, Catalysis S.L. (Madrid, Spain) and the Regional Development Funding Program (FEDER) “A way to make Europe”.Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Instituto de Salud Carlos IIIJunta de Castilla y LeónFundación CRIS contra el CáncerEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/381449reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//BFU2015-71371-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-115605RB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/nu16152416https://doi.org/10.3390/nu16152416Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3814492026-05-22T06:33:51Z
dc.title.none.fl_str_mv Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer
title Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer
spellingShingle Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer
Almaraz Postigo, Sheila
Ovarian cancer
OOS
Antioxidants
DNA damage
Cell death
title_short Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer
title_full Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer
title_fullStr Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer
title_full_unstemmed Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer
title_sort Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer
dc.creator.none.fl_str_mv Almaraz Postigo, Sheila
Sanz, Eduardo
Pandiella, Atanasio
Díaz-Rodríguez, Elena
author Almaraz Postigo, Sheila
author_facet Almaraz Postigo, Sheila
Sanz, Eduardo
Pandiella, Atanasio
Díaz-Rodríguez, Elena
author_role author
author2 Sanz, Eduardo
Pandiella, Atanasio
Díaz-Rodríguez, Elena
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Instituto de Salud Carlos III
Junta de Castilla y León
Fundación CRIS contra el Cáncer
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Ovarian cancer
OOS
Antioxidants
DNA damage
Cell death
topic Ovarian cancer
OOS
Antioxidants
DNA damage
Cell death
description Ovarian cancer is the most fatal of all the reproductive cancers within the female population, mainly due to its late diagnosis that limits surgery and medical treatment. Classically, ovarian cancer therapy has included conventional chemotherapy, and other therapeutic approaches are now being used to treat these patients, but the outcomes of the disease are still poor. Therefore, new strategies are needed to improve life expectancy and life quality of ovarian cancer patients. Considering that, we investigated the effect of the nutritional supplement Ocoxin Oral Solution (OOS) in ovarian cancer models. OOS contains several nutritional supplements, some of them with demonstrated antitumoral action. In vitro studies showed that OOS inhibited the proliferation of several ovarian cancer cell lines, especially of those representative of the endometrioid subtype, in a time- and dose-dependent manner. A fast cell death induction after OOS treatment was observed, and when the molecular mechanisms leading to this effect were investigated, an activation of the DNA damage checkpoint was detected, as shown by activation (phosphorylation) of CHK1 and CHK2 kinases that was followed by the phosphorylation of the target protein histone H2AX. When tested in animal models of ovarian cancer, OOS reduced tumor growth without any observed secondary effects. Moreover, such reduction in tumor proliferation was caused by the induction of DNA damage as corroborated by the in vivo phosphorylation of CHK2 and Histone H2AX. Finally, OOS potentiated the action of carboplatin or olaparib, the standard of care treatments used in ovarian clinics, opening the possibility of including OOS in combination with those standard of care agents in patients with ovarian cancer.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/381449
url http://hdl.handle.net/10261/381449
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO//BFU2015-71371-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-115605RB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/nu16152416
https://doi.org/10.3390/nu16152416

dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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