Su-Jung Choi , Ji-Hoon Kim , Hyun-Ji Kim , Dong-Guk Park , Bohwan Jin , Won Woo Lee , Kyoung-Ok Hong , Sak Lee , Thantrira Porntaveetus , Jae-Jin Cho , Seong-Doo Hong , Sung-Dae Cho
{"title":"鬼臼毒素诱发有丝分裂突变诱导口腔鳞癌细胞凋亡。","authors":"Su-Jung Choi , Ji-Hoon Kim , Hyun-Ji Kim , Dong-Guk Park , Bohwan Jin , Won Woo Lee , Kyoung-Ok Hong , Sak Lee , Thantrira Porntaveetus , Jae-Jin Cho , Seong-Doo Hong , Sung-Dae Cho","doi":"10.1016/j.archoralbio.2025.106396","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>This study investigated the relationship between mitotic catastrophe (MC) and apoptosis in oral squamous cell carcinoma (OSCC) using podophyllotoxin (PPT), a natural compound with antimitotic properties.</div></div><div><h3>Design</h3><div>We evaluated the concentration-dependent effects of PPT on cell proliferation (CCK-8 and soft agar assays) and morphology (transmission electron microscopy). Mechanistic insights were obtained by assessing DNA damage (western blotting), cell cycle progression (sub-G<sub>1</sub> analysis), and apoptosis-related protein activation in both 2D and 3D spheroid models of HSC-3 oral squamous carcinoma cells.</div></div><div><h3>Results</h3><div>PPT exerted pronounced inhibitory effects on cell proliferation and anchorage-independent growth accompanied by morphological indications of MC, such as enlarged multinucleated cells. DNA damage induced by PPT resulted in ataxia telangiectasia mutated kinase and checkpoint kinase 2 activation, leading to G<sub>2</sub>/M arrest and cyclin B1upregulation. Importantly, PPT-induced MC was followed by apoptosis, as evidenced by an increased sub-G<sub>1</sub> population, Annexin V positivity, and caspase activation. Mitochondrial dysfunction, as indicated by altered membrane potential and enhanced Bax expression, underscored the apoptotic process. Caspase-2 activation emerged as a pivotal event, cleaving Bid and establishing a link between MC and the intrinsic apoptotic pathway. The effects were consistent across both 2D and 3D models, suggesting a robust therapeutic potential.</div></div><div><h3>Conclusions</h3><div>This study provides compelling evidence supporting the potential therapeutic significance of inducing MC-mediated apoptosis in OSCC. The results underscore the role of PPT and its derivatives, such as etoposide and teniposide, in targeting rapidly dividing cancer cells through interference with mitotic progression, offering insights into novel therapeutic strategies for oral cancer.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"179 ","pages":"Article 106396"},"PeriodicalIF":2.1000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Triggering mitotic catastrophe by podophyllotoxin induces apoptosis in oral squamous cell carcinoma\",\"authors\":\"Su-Jung Choi , Ji-Hoon Kim , Hyun-Ji Kim , Dong-Guk Park , Bohwan Jin , Won Woo Lee , Kyoung-Ok Hong , Sak Lee , Thantrira Porntaveetus , Jae-Jin Cho , Seong-Doo Hong , Sung-Dae Cho\",\"doi\":\"10.1016/j.archoralbio.2025.106396\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>This study investigated the relationship between mitotic catastrophe (MC) and apoptosis in oral squamous cell carcinoma (OSCC) using podophyllotoxin (PPT), a natural compound with antimitotic properties.</div></div><div><h3>Design</h3><div>We evaluated the concentration-dependent effects of PPT on cell proliferation (CCK-8 and soft agar assays) and morphology (transmission electron microscopy). Mechanistic insights were obtained by assessing DNA damage (western blotting), cell cycle progression (sub-G<sub>1</sub> analysis), and apoptosis-related protein activation in both 2D and 3D spheroid models of HSC-3 oral squamous carcinoma cells.</div></div><div><h3>Results</h3><div>PPT exerted pronounced inhibitory effects on cell proliferation and anchorage-independent growth accompanied by morphological indications of MC, such as enlarged multinucleated cells. DNA damage induced by PPT resulted in ataxia telangiectasia mutated kinase and checkpoint kinase 2 activation, leading to G<sub>2</sub>/M arrest and cyclin B1upregulation. Importantly, PPT-induced MC was followed by apoptosis, as evidenced by an increased sub-G<sub>1</sub> population, Annexin V positivity, and caspase activation. Mitochondrial dysfunction, as indicated by altered membrane potential and enhanced Bax expression, underscored the apoptotic process. Caspase-2 activation emerged as a pivotal event, cleaving Bid and establishing a link between MC and the intrinsic apoptotic pathway. The effects were consistent across both 2D and 3D models, suggesting a robust therapeutic potential.</div></div><div><h3>Conclusions</h3><div>This study provides compelling evidence supporting the potential therapeutic significance of inducing MC-mediated apoptosis in OSCC. The results underscore the role of PPT and its derivatives, such as etoposide and teniposide, in targeting rapidly dividing cancer cells through interference with mitotic progression, offering insights into novel therapeutic strategies for oral cancer.</div></div>\",\"PeriodicalId\":8288,\"journal\":{\"name\":\"Archives of oral biology\",\"volume\":\"179 \",\"pages\":\"Article 106396\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of oral biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0003996925002249\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of oral biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0003996925002249","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
Triggering mitotic catastrophe by podophyllotoxin induces apoptosis in oral squamous cell carcinoma
Objective
This study investigated the relationship between mitotic catastrophe (MC) and apoptosis in oral squamous cell carcinoma (OSCC) using podophyllotoxin (PPT), a natural compound with antimitotic properties.
Design
We evaluated the concentration-dependent effects of PPT on cell proliferation (CCK-8 and soft agar assays) and morphology (transmission electron microscopy). Mechanistic insights were obtained by assessing DNA damage (western blotting), cell cycle progression (sub-G1 analysis), and apoptosis-related protein activation in both 2D and 3D spheroid models of HSC-3 oral squamous carcinoma cells.
Results
PPT exerted pronounced inhibitory effects on cell proliferation and anchorage-independent growth accompanied by morphological indications of MC, such as enlarged multinucleated cells. DNA damage induced by PPT resulted in ataxia telangiectasia mutated kinase and checkpoint kinase 2 activation, leading to G2/M arrest and cyclin B1upregulation. Importantly, PPT-induced MC was followed by apoptosis, as evidenced by an increased sub-G1 population, Annexin V positivity, and caspase activation. Mitochondrial dysfunction, as indicated by altered membrane potential and enhanced Bax expression, underscored the apoptotic process. Caspase-2 activation emerged as a pivotal event, cleaving Bid and establishing a link between MC and the intrinsic apoptotic pathway. The effects were consistent across both 2D and 3D models, suggesting a robust therapeutic potential.
Conclusions
This study provides compelling evidence supporting the potential therapeutic significance of inducing MC-mediated apoptosis in OSCC. The results underscore the role of PPT and its derivatives, such as etoposide and teniposide, in targeting rapidly dividing cancer cells through interference with mitotic progression, offering insights into novel therapeutic strategies for oral cancer.
期刊介绍:
Archives of Oral Biology is an international journal which aims to publish papers of the highest scientific quality in the oral and craniofacial sciences. The journal is particularly interested in research which advances knowledge in the mechanisms of craniofacial development and disease, including:
Cell and molecular biology
Molecular genetics
Immunology
Pathogenesis
Cellular microbiology
Embryology
Syndromology
Forensic dentistry