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Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway
Mansour, Suzan Mohamed; Ibrahim, Rasha Youssef Mohammed.
  • Mansour, Suzan Mohamed; Cairo University. Faculty of Pharmacy. Department of Pharmacology and Toxicology. Cairo. EG
  • Ibrahim, Rasha Youssef Mohammed; Atomic Energy Authority. Nuclear Research Centre. Department of Radioisotopes. Cairo. EG
Braz. J. Pharm. Sci. (Online) ; 58: e19922, 2022. tab, graf
Article in English | LILACS | ID: biblio-1384022
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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Full text: Available Index: LILACS (Americas) Main subject: Carcinoma, Ehrlich Tumor / Neoplasms Limits: Animals Language: English Journal: Braz. J. Pharm. Sci. (Online) Journal subject: Farmacologia / Terapˆutica / Toxicologia Year: 2022 Type: Article Affiliation country: Egypt Institution/Affiliation country: Atomic Energy Authority/EG / Cairo University/EG

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Full text: Available Index: LILACS (Americas) Main subject: Carcinoma, Ehrlich Tumor / Neoplasms Limits: Animals Language: English Journal: Braz. J. Pharm. Sci. (Online) Journal subject: Farmacologia / Terapˆutica / Toxicologia Year: 2022 Type: Article Affiliation country: Egypt Institution/Affiliation country: Atomic Energy Authority/EG / Cairo University/EG