{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T11:45:33Z","timestamp":1781523933517,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science and Technology of Jilin Province, China","award":["20220204022YY"],"award-info":[{"award-number":["20220204022YY"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cervical cancer remains a major threat to women\u2019s health, with advanced cases often exhibiting recurrence and metastasis due to cancer stem cells driving therapy resistance. This study evaluated fenbendazole (FBZ), a repurposed veterinary anthelmintic, for its antitumor activity dual targeting cervical cancer cells (CCCs) and cervical cancer stem cells (CCSCs). CD133+CD44+ CCSCs were isolated from HeLa and C-33 A cell lines via immunomagnetic sorting and validated for stemness. Cell proliferation, cell cycle and apoptosis, and protein expression were detected by MST assay, flow cytometry, and Western blot analysis, respectively. FBZ dose-dependently inhibited proliferation, induced G2\/M arrest, and triggered apoptosis in both CCCs and CCSCs. Mechanistically, FBZ upregulated cyclin B1 and phosphorylation of cdc25C-Ser198, while downregulating Wee1, phosphorylation of CDK1, and phosphorylation of cdc25C-Ser216, collectively enforcing G2\/M blockade. In vivo, FBZ (100 mg\/kg) significantly suppressed tumor growth in xenograft models without weight loss, contrasting with cisplatin-induced toxicity. Survival analysis revealed 100% survival in FBZ-treated mice versus 40% in cisplatin and 0% in untreated controls. These findings demonstrate FBZ\u2019s unique ability to simultaneously target bulk tumor cells and therapy-resistant CCSCs via cell cycle disruption, supported by its preclinical safety and efficacy, positioning it as a promising therapeutic candidate for cervical cancer.<\/jats:p>","DOI":"10.3390\/molecules30112377","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T04:27:58Z","timestamp":1748579278000},"page":"2377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Fenbendazole Exhibits Antitumor Activity Against Cervical Cancer Through Dual Targeting of Cancer Cells and Cancer Stem Cells: Evidence from In Vitro and In Vivo Models"],"prefix":"10.3390","volume":"30","author":[{"given":"Xi","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Fujin Road 1266, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4021-1067","authenticated-orcid":false,"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Fujin Road 1266, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Fujin Road 1266, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyue","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Fujin Road 1266, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Fujin Road 1266, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8020-3921","authenticated-orcid":false,"given":"Zhongyi","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Fujin Road 1266, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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