Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Pharmaceutical Sciences |
Texto Completo: | https://www.revistas.usp.br/bjps/article/view/204301 |
Resumo: | Angiotensin-II (AgII) is thought to be crucial for tumor growth and progression. Moreover, hydrogen sulfide (H2S) performs a controversial action in cancer pathology. Zofenopril (ZF) is an angiotensin-converting enzyme (ACE) inhibitor with H2S donating properties. Hence, this study aims at investigating the tumor suppressor activity of ZF and elucidating the involved trajectories in Ehrlich’s solid tumor (EST)-bearing mice. EST was induced by the intradermal injection of Ehrlich’s ascites carcinoma cells into femoral region. All parameters were assessed after 28 days post-inoculation or one-week thereafter. ZF treatment resulted in significant reduction of tumor weights with marked decrease in IL-6 and VEGF levels in serum, and tumor Ag II and CEA contents. Additionally, the administration of ZF downregulated the tumor gene expression of cyclin-D, ACE-1, and Bcl2 and upregulated the proapoptotic gene, BAX. Moreover, ZF increased CBS gene expression, which is a major contributor to cellular H2S production. In addition, ZF was able to reduce the protein expression of PI3K, pAKT, pGSK-3β, and NFκB. Our study has provided novel insights into the possible mechanisms by which ZF may produce its tumor defeating properties. These intersecting trajectories involve the interference between PI3K/Akt and CBS signaling pathways. |
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Brazilian Journal of Pharmaceutical Sciences |
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Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathwayZofenoprilAngiotensin IICancerPI3K/AktHydrogen sulfideCystathionine beta synthaseAngiotensin-II (AgII) is thought to be crucial for tumor growth and progression. Moreover, hydrogen sulfide (H2S) performs a controversial action in cancer pathology. Zofenopril (ZF) is an angiotensin-converting enzyme (ACE) inhibitor with H2S donating properties. Hence, this study aims at investigating the tumor suppressor activity of ZF and elucidating the involved trajectories in Ehrlich’s solid tumor (EST)-bearing mice. EST was induced by the intradermal injection of Ehrlich’s ascites carcinoma cells into femoral region. All parameters were assessed after 28 days post-inoculation or one-week thereafter. ZF treatment resulted in significant reduction of tumor weights with marked decrease in IL-6 and VEGF levels in serum, and tumor Ag II and CEA contents. Additionally, the administration of ZF downregulated the tumor gene expression of cyclin-D, ACE-1, and Bcl2 and upregulated the proapoptotic gene, BAX. Moreover, ZF increased CBS gene expression, which is a major contributor to cellular H2S production. In addition, ZF was able to reduce the protein expression of PI3K, pAKT, pGSK-3β, and NFκB. Our study has provided novel insights into the possible mechanisms by which ZF may produce its tumor defeating properties. These intersecting trajectories involve the interference between PI3K/Akt and CBS signaling pathways.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas2022-11-23info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/bjps/article/view/20430110.1590/s2175-97902022e19922Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)Brazilian Journal of Pharmaceutical Sciences; v. 58 (2022)Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)2175-97901984-8250reponame:Brazilian Journal of Pharmaceutical Sciencesinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/bjps/article/view/204301/196407Copyright (c) 2022 Brazilian Journal of Pharmaceutical Scienceshttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessMohamed Mansour, SuzanYoussef Mohammed Ibrahim, Rasha2023-04-10T19:14:04Zoai:revistas.usp.br:article/204301Revistahttps://www.revistas.usp.br/bjps/indexPUBhttps://old.scielo.br/oai/scielo-oai.phpbjps@usp.br||elizabeth.igne@gmail.com2175-97901984-8250opendoar:2023-04-10T19:14:04Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway |
title |
Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway |
spellingShingle |
Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway Mohamed Mansour, Suzan Zofenopril Angiotensin II Cancer PI3K/Akt Hydrogen sulfide Cystathionine beta synthase |
title_short |
Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway |
title_full |
Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway |
title_fullStr |
Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway |
title_full_unstemmed |
Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway |
title_sort |
Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway |
author |
Mohamed Mansour, Suzan |
author_facet |
Mohamed Mansour, Suzan Youssef Mohammed Ibrahim, Rasha |
author_role |
author |
author2 |
Youssef Mohammed Ibrahim, Rasha |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Mohamed Mansour, Suzan Youssef Mohammed Ibrahim, Rasha |
dc.subject.por.fl_str_mv |
Zofenopril Angiotensin II Cancer PI3K/Akt Hydrogen sulfide Cystathionine beta synthase |
topic |
Zofenopril Angiotensin II Cancer PI3K/Akt Hydrogen sulfide Cystathionine beta synthase |
description |
Angiotensin-II (AgII) is thought to be crucial for tumor growth and progression. Moreover, hydrogen sulfide (H2S) performs a controversial action in cancer pathology. Zofenopril (ZF) is an angiotensin-converting enzyme (ACE) inhibitor with H2S donating properties. Hence, this study aims at investigating the tumor suppressor activity of ZF and elucidating the involved trajectories in Ehrlich’s solid tumor (EST)-bearing mice. EST was induced by the intradermal injection of Ehrlich’s ascites carcinoma cells into femoral region. All parameters were assessed after 28 days post-inoculation or one-week thereafter. ZF treatment resulted in significant reduction of tumor weights with marked decrease in IL-6 and VEGF levels in serum, and tumor Ag II and CEA contents. Additionally, the administration of ZF downregulated the tumor gene expression of cyclin-D, ACE-1, and Bcl2 and upregulated the proapoptotic gene, BAX. Moreover, ZF increased CBS gene expression, which is a major contributor to cellular H2S production. In addition, ZF was able to reduce the protein expression of PI3K, pAKT, pGSK-3β, and NFκB. Our study has provided novel insights into the possible mechanisms by which ZF may produce its tumor defeating properties. These intersecting trajectories involve the interference between PI3K/Akt and CBS signaling pathways. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-11-23 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.revistas.usp.br/bjps/article/view/204301 10.1590/s2175-97902022e19922 |
url |
https://www.revistas.usp.br/bjps/article/view/204301 |
identifier_str_mv |
10.1590/s2175-97902022e19922 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://www.revistas.usp.br/bjps/article/view/204301/196407 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences https://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences https://creativecommons.org/licenses/by/4.0 |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas |
publisher.none.fl_str_mv |
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas |
dc.source.none.fl_str_mv |
Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022) Brazilian Journal of Pharmaceutical Sciences; v. 58 (2022) Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022) 2175-9790 1984-8250 reponame:Brazilian Journal of Pharmaceutical Sciences instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Brazilian Journal of Pharmaceutical Sciences |
collection |
Brazilian Journal of Pharmaceutical Sciences |
repository.name.fl_str_mv |
Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
bjps@usp.br||elizabeth.igne@gmail.com |
_version_ |
1787713373379493888 |