{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T15:29:02Z","timestamp":1775921342767,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Lung cancer has risen to the top of the list of cancer\u2010related deaths worldwide. Aliskiren is a direct renin inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>This study aims to investigate the impact of cell signaling of\u00a0Renin\u2010Angiotensin\u00a0system\u00a0(RAS)\/NF\u2010\u03baB on lung cancer by investigating the potential therapeutic effects of aliskiren for lung cancer treatment in urethane\u2010induced lung cancer in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male BALB\/c mice were randomly assigned to one of five treatment groups for 150\u2009days, including (1) normal control; (2) aliskiren (25\u2009mg\/kg\/i.p) daily, (3) urethane at a dose of 1.5\u2009g\/kg (i.p) at Day 1 and 60 (nonsmall cell lung cancer[NSCLC] group) (4) NSCLC mice received carboplatin (15\u2009mg\/kg\/i.p) every other day for the last 4 successive weeks and (5) NSCLC mice treated with aliskiren daily. Tumor size was determined based on blood sampling, and lungs were isolated for biochemical analysis, western blot analysis assay, and histopathological examination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Urethane demonstrated significant changes in all biochemical and molecular parameters and histological patterns. Aliskiren\u2010treated mice had significantly lower levels of NF\u2010\u03baB p65, Bcl\u20102, cyclin D1, ICAM\u20101, MMP\u20102, and Nrf2, with an increase in the catalytic activity of caspase\u20103 due to its RAS inhibitory mechanism. The combined urethane administration with aliskiren demonstrated a significant improvement in the histopathological examination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>RAS\/NF\u2010B cell signaling is a potential therapeutic target for preventing and treating lung adenocarcinoma, evidenced by the fundamental cytotoxic mechanism and attenuation of metastasis and angiogenesis induced by the treatment of NSCLC mice with aliskiren.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbt.23162","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T10:16:04Z","timestamp":1657707364000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel therapeutic modalities target cell signaling of Renin\u2010Angiotensin\u00a0system\/NF\u2010\u03baB\u2010induced cell cycle arrest and apoptosis in urethane\u2010induced lung cancer in mice: An in vivo study"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9142-1780","authenticated-orcid":false,"given":"Marwa M.","family":"Khalaf","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Beni\u2010Suef University Beni\u2010Suef Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amira M.","family":"Abo\u2010Youssef","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Beni\u2010Suef University Beni\u2010Suef Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina N.","family":"Malak","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Beni\u2010Suef University Beni\u2010Suef Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-025X","authenticated-orcid":false,"given":"Mohamed A.","family":"Hamzawy","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Fayoum University Fayoum Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2019.10.001"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061604"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/2314808X.2021.2022924"},{"key":"e_1_2_10_5_1","first-page":"1514","volume":"365","author":"Maconachie R.","year":"2019","journal-title":"BMJ"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8DT00838H"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0064"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107527"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061457"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1470320313496858"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-19-0314"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705316104"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-3578"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.2741\/3782"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2015.05.001"},{"issue":"4","key":"e_1_2_10_16_1","first-page":"468","volume":"36","author":"Chao\u2010Yi W.","year":"2016","journal-title":"Basic Clin. 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