{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:25:11Z","timestamp":1791725111635,"version":"4.3.4"},"reference-count":68,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2023R304"],"award-info":[{"award-number":["PNURSP2023R304"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["34748"],"award-info":[{"award-number":["34748"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science, Technology and Innovation Funding Authority (STDF)","award":["PNURSP2023R304"],"award-info":[{"award-number":["PNURSP2023R304"]}]},{"name":"Science, Technology and Innovation Funding Authority (STDF)","award":["34748"],"award-info":[{"award-number":["34748"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The study evaluated the antitumor efficacy of APAN, \u201csynthesized indoloquinoline analog derived from the parent neocryptolepine isolated from the roots of Cryptolepis sanguinolenta\u201d, versus the chemotherapeutic drug etoposide (ETO) in Ehrlich solid tumor (EST)-bearing female mice as well as its protective effect against etoposide-triggered hepatic disorders. APAN showed an ameliorative activity against Ehrlich solid tumor and hepatic toxicity, and the greatest improvement was found in the combined treatment of APAN with ETO. The results indicated that EST altered the levels of tumor markers (AFP, CEA, and anti-dsDNA) and liver biomarker function (ALT, AST, ALP, ALB, and T. protein). Furthermore, EST elevated CD68 and anti-survivin proteins immuno-expressions in the solid tumor and liver tissue. Molecular docking studies were demonstrated to investigate their affinity for both TNF-\u03b1 and topoisomerase II as target proteins, as etoposide is based on the inhibition of topoisomerase II, and TNF-\u03b1 is quite highly expressed in the solid tumor and liver tissues of EST-bearing animals, which prompted the authors\u2019 interest to explore APAN affinity to its binding site. Treatment of mice bearing EST with APAN and ETO nearly regularized serum levels of the altered parameters and ameliorated the impact of EST on the tissue structure of the liver better than that by treatment with each of them separately.<\/jats:p>","DOI":"10.3390\/cells12071024","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T01:41:34Z","timestamp":1679967694000},"page":"1024","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Impact of Synthesized Indoloquinoline Analog to Isolates from Cryptolepis sanguinolenta on Tumor Growth Inhibition and Hepatotoxicity in Ehrlich Solid Tumor-Bearing Female Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Amany E.","family":"Nofal","sequence":"first","affiliation":[{"name":"Zoology Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1160-5040","authenticated-orcid":false,"given":"Elshaymaa I.","family":"Elmongy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engy Abo","family":"Hassan","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9722-3603","authenticated-orcid":false,"given":"Ehab","family":"Tousson","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Science, Tanta University, Tanta 31511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7515-2824","authenticated-orcid":false,"given":"Abdullah A. S.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim El Tantawy","family":"El Sayed","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1406-282X","authenticated-orcid":false,"given":"Reem","family":"Binsuwaidan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar","family":"Sakr","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nrendo.2010.87","article-title":"Environmental causes of cancer: Endocrine disruptors as carcinogens","volume":"6","author":"Soto","year":"2010","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20600","DOI":"10.1007\/s11356-016-7220-1","article-title":"The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis, and oxidative stress caused by amethopterin","volume":"23","author":"Tousson","year":"2016","journal-title":"Environ. Sci. Pollut. 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