{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:11:36Z","timestamp":1779081096209,"version":"3.51.4"},"reference-count":61,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"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":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cucurbitacin\u2010E\u2010glucoside (CEG), a natural compound from the Cucurbitaceae family, has shown anti\u2010proliferative effects on various human cancer cell lines and is believed to inhibit the peroxisome proliferative activated receptor gamma (PPAR\u03b3) signaling pathway. We aimed to investigate the anti\u2010cancer effects of CEG in a mouse model of Ehrlich ascites carcinoma (EAC) and its capacity to improve the efficacy of tamoxifen (TAM) treatment. By examining the in vivo and in silico interactions between CEG and tamoxifen with PPAR\u03b3, this study presents a novel approach to cancer management.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CEG (50\u2009mg\/k.g.b.w.) and TAM (20\u2009mg\/k.g.b.w.) were administered individually and\/or in combination with the EAC\u2010bearing mice. After 4 weeks of treatment, tumor weight and volume were measured. Additionally, inflammation and oxidative stress biomarkers, as well as apoptotic and antiapoptotic genes, were evaluated using ELISA and qRT\u2010PCR. DNA cell cycle analysis of cancer cells was also performed using flow cytometry. To elucidate the molecular mechanism of CEG, PPAR\u03b3 and NF\u2010\u03baB, the key transcription factor, were studied using Western blot and molecular docking studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Oral administration of CEG and tamoxifen individually and\/or in combination led to significant decreases in tumor volume and weight. Additionally, the drug combination led to significant decreases in the proliferation index S phase and G2 phase. Moreover, treatment of CEG induces the expression of apoptotic PPAR\u03b1 and PPAR\u03b3 as well as inhibits the expression of antiapoptotic Bcl\u20102 and HIF\u20101\u0391 genes. Meanwhile, combining CEG with TAM showed a significant increase in liver GSH, CAT, SOD, NP\u2010SH, and protein as well as significant decreases in levels of the plasma inflammatory markers IL\u20102, IL\u20106, TGF\u2010 \u03b21, and the angiogenesis marker VEGF\u2010C. Western blot analyses showed that CEG alone induced 2.8\u2010fold PPAR\u03b3 upregulation and 1.9\u2010fold NF\u2010\u03baB suppression (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) compared to the EAC group. Molecular docking analyses of CEG within the ligand\u2010binding domains of the PPAR\u03b3 and the inflammation transcription factor NF\u2010KB proteins demonstrated comparable binding affinities to the PPAR\u03b3 agonist Rosiglitazone and the NF\u2010KB inhibitor MG\u2010132, corroborating results obtained in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings show that CEG therapy activates apoptotic PPAR\u03b1 and PPAR\u03b3 genes and suppresses anti\u2010apoptotic Bcl\u20102 and HIF\u20101\u0391 genes, while reducing the oxidative stress and inflammation in EAC cells through a mechanism involving inhibition of NF\u2010k\u03b2. Finally, CEG creates a safe and synergistic environment that amplifies the therapeutic benefits of tamoxifen.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbt.70540","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T07:18:01Z","timestamp":1759216681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cucurbitacin\u2010E\u2010Glucoside Augments Tamoxifen's Anticancer Efficacy by Targeting PPAR\u03b3 and NF\u2010kB: In Vivo and In Silico Studies"],"prefix":"10.1002","volume":"39","author":[{"given":"Yasmin","family":"Sabry","sequence":"first","affiliation":[{"name":"Molecular Biology Department, Genetic Engineering and Biotechnology Institute University of Sadat City Sadat City Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed A.","family":"Hussein","sequence":"additional","affiliation":[{"name":"Biotechnology Department, Faculty of Applied Health Sciences Technology October 6 University First 6th of October Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-6847","authenticated-orcid":false,"given":"Mohamed F.","family":"Elshal","sequence":"additional","affiliation":[{"name":"Molecular Biology Department, Genetic Engineering and Biotechnology Institute University of Sadat City Sadat City Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.21635"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22179451"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.6026\/97320630012135"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0226150"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/704165"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.682762"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1691"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2024.14294"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570163817666200518081955"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.5681\/apb.2014.062"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.5772\/intechopen.94040"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.0c00144"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-13-52"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.4103\/0973-7847.156314"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(20)30058-3"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.31303"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11327"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23326"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.65875"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208470"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e3283541384"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2019.1635149"},{"issue":"8","key":"e_1_2_10_25_1","first-page":"554","article-title":"The Solid Phase of the Ehrlich Ascites Tumor in Mice","volume":"14","author":"Baillif R. 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