Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway
Braz. J. Pharm. Sci. (Online)
; 58: e19922, 2022. tab, graf
Article
em En
| LILACS
| ID: biblio-1384022
Biblioteca responsável:
BR40.1
Localização: BR40.1
ABSTRACT
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-3ß, 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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Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Carcinoma de Ehrlich
/
Neoplasias
Limite:
Animals
Idioma:
En
Revista:
Braz. J. Pharm. Sci. (Online)
Assunto da revista:
Farmacologia
/
Teraputica
/
Toxicologia
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Egito
País de publicação:
Brasil