{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:40:08Z","timestamp":1741754408074,"version":"3.38.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST 111\u20102314\u2010B\u2010371\u2010008\u2010MY3"],"award-info":[{"award-number":["MOST 111\u20102314\u2010B\u2010371\u2010008\u2010MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007632","name":"Changhua Christian Hospital","doi-asserted-by":"publisher","award":["112\u2010CCH\u2010ICO\u2010151"],"award-info":[{"award-number":["112\u2010CCH\u2010ICO\u2010151"]}],"id":[{"id":"10.13039\/501100007632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The prevalence of oral squamous cell carcinoma (OSCC) is increasing worldwide mainly due to poor oral hygiene and unrestricted lifestyle. Advanced\u2010stage OSCC is associated with poor prognosis and a 5\u2010year survival rate of only 30%\u201350%. The present study was designed to investigate the anticancer effect and mode of action of <jats:italic>Glycyrrhiza<\/jats:italic>\u2010derived semilicoisoflavone B (SFB) in 5\u2010fluorourasil (5FU)\u2010resistant human OSCC cell lines. The study findings revealed that SFB significantly reduces OSCC cell viability and colony formation ability by arresting cell cycle at the G2\/M and S phases and reducing the expressions of key cell cycle regulators including cyclin A, cyclin B, CDC2, and CDK2. The compound caused a significant induction in the percentage of nuclear condensation and apoptotic cells in OSCC. Regarding pro\u2010apoptotic mode of action, SFB was found to increase Fas\u2010associated death domain and death receptor 5 expressions and reduce decoy receptor 2 expression, indicating involvement of extrinsic pathway. Moreover, SFB was found to increase pro\u2010apoptotic Bim expression and reduce anti\u2010apoptotic Bcl\u20102 and Bcl\u2010xL expressions, indicating involvement of intrinsic pathway. Moreover, SFB\u2010mediated induction in cleaved caspases 3, 8, and 9 and cleaved poly(ADP\u2010ribose) polymerase confirmed the induction of caspase\u2010mediated apoptotic pathways. Regarding upstream signaling pathway, SFB was found to reduce extracellular signal regulated kinase 1\/2 (ERK) phosphorylation to execute its pro\u2010apoptotic activity. The Human Apoptotic Array findings revealed that SFB suppresses claspin expression, which in turn caused reduced phosphorylation of ATR, checkpoint kinase 1 (Chk1), Wee1, and CDC25C, indicating disruption of ATR\u2010Chk1 signaling pathway by SFB. Taken together, these findings indicate that SFB acts as a potent anticancer compound against 5FU\u2010resistant OSCC by modulating mitogen\u2010activated protein kinase (MAPK) and ATR\u2010Chk1 signaling pathways.<\/jats:p>","DOI":"10.1002\/tox.24107","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T11:40:19Z","timestamp":1704886819000},"page":"2417-2428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Semilicoisoflavone B induces oral cancer cell apoptosis by targeting claspin and <scp>ATR\u2010Chk1<\/scp> signaling pathways"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9726-3234","authenticated-orcid":false,"given":"Ming\u2010Ju","family":"Hsieh","sequence":"first","affiliation":[{"name":"Oral Cancer Research Center Changhua Christian Hospital  Changhua Taiwan"},{"name":"Doctoral Program in Tissue Engineering and Regenerative Medicine, College of Medicine National Chung Hsing University  Taichung Taiwan"},{"name":"Graduate Institute of Biomedical Sciences China Medical University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia\u2010Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Oral Cancer Research Center Changhua Christian Hospital  Changhua Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Sheng","family":"Lo","sequence":"additional","affiliation":[{"name":"Oral Cancer Research Center Changhua Christian Hospital  Changhua Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Ching","family":"Chuang","sequence":"additional","affiliation":[{"name":"Oral Cancer Research Center Changhua Christian Hospital  Changhua Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin\u2010Yu","family":"Ho","sequence":"additional","affiliation":[{"name":"Oral Cancer Research Center Changhua Christian Hospital  Changhua Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mu\u2010Kuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Changhua Christian Hospital  Changhua Taiwan"},{"name":"Department of Post\u2010Baccalaureate Medicine, College of Medicine National Chung Hsing University  Taichung 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