Autophagy-related biological targets and network mechanisms of juglone against bladder cancer
Abstract Objective This study aimed to explore juglone’s mechanism in inducing autophagy and apoptosis in bladder cancer (BLCA) via network pharmacology and experimental validation. Methods Juglone’s effects on BLCA cell proliferation, apoptosis, and autophagy were assessed using CCK-8, flow cytomet...
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| Format: | Article |
| Language: | English |
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Springer
2025-06-01
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| Series: | Journal of Cancer Research and Clinical Oncology |
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| Online Access: | https://doi.org/10.1007/s00432-025-06243-5 |
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| author | Yuanfeng Zhang Enguang Yang Xinyu Zhang Ze Zhang Guoxin Huang Baoyuan Tang Chaohu Chen Longhui Lai Zixu Pei Yonghai Zhang Zhiping Wang |
| author_facet | Yuanfeng Zhang Enguang Yang Xinyu Zhang Ze Zhang Guoxin Huang Baoyuan Tang Chaohu Chen Longhui Lai Zixu Pei Yonghai Zhang Zhiping Wang |
| author_sort | Yuanfeng Zhang |
| collection | DOAJ |
| description | Abstract Objective This study aimed to explore juglone’s mechanism in inducing autophagy and apoptosis in bladder cancer (BLCA) via network pharmacology and experimental validation. Methods Juglone’s effects on BLCA cell proliferation, apoptosis, and autophagy were assessed using CCK-8, flow cytometry, transmission electron microscopy, and Western blotting. Network pharmacology, molecular docking, and dynamics simulations identified key targets. In vivo validation employed H&E, immunohistochemical, and TUNEL staining. Results Juglone suppressed T24 and UMUC-3 cell proliferation, enhanced autophagy markers, and induced apoptosis. Network analysis identified 108 shared targets, with AKT1, CASP3, and TP53 as core nodes. Pathway enrichment implicated the PI3K/Akt signalling pathway, supported by molecular docking. Autophagy inhibition reduced juglone-induced apoptosis, confirming autophagic death’s role. Conclusions Juglone triggers BLCA autophagy via PI3K/AKT/mTOR, upregulates apoptotic proteins, and activates caspase 3, promoting apoptosis. |
| format | Article |
| id | doaj-art-738adfb1a9fc43be8817892d444d8e1d |
| institution | DOAJ |
| issn | 1432-1335 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Cancer Research and Clinical Oncology |
| spelling | doaj-art-738adfb1a9fc43be8817892d444d8e1d2025-08-20T03:04:16ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-06-01151611610.1007/s00432-025-06243-5Autophagy-related biological targets and network mechanisms of juglone against bladder cancerYuanfeng Zhang0Enguang Yang1Xinyu Zhang2Ze Zhang3Guoxin Huang4Baoyuan Tang5Chaohu Chen6Longhui Lai7Zixu Pei8Yonghai Zhang9Zhiping Wang10Institute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, The Second Hospital & Clinical Medical School, Lanzhou UniversityInstitute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, The Second Hospital & Clinical Medical School, Lanzhou UniversityInstitute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, The Second Hospital & Clinical Medical School, Lanzhou UniversityInstitute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, The Second Hospital & Clinical Medical School, Lanzhou UniversityClinical Research Center, Shantou Central HospitalThe Second Clinical Medical School, Lanzhou UniversityInstitute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, The Second Hospital & Clinical Medical School, Lanzhou UniversityInstitute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, The Second Hospital & Clinical Medical School, Lanzhou UniversityAndrology Center, Department of Urology, Peking University First Hospital, Peking UniversityDepartment of Urology, Shantou Central Hospital, Shantou Key Laboratory of Basic and Translational Research of Malignant TumorInstitute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, The Second Hospital & Clinical Medical School, Lanzhou UniversityAbstract Objective This study aimed to explore juglone’s mechanism in inducing autophagy and apoptosis in bladder cancer (BLCA) via network pharmacology and experimental validation. Methods Juglone’s effects on BLCA cell proliferation, apoptosis, and autophagy were assessed using CCK-8, flow cytometry, transmission electron microscopy, and Western blotting. Network pharmacology, molecular docking, and dynamics simulations identified key targets. In vivo validation employed H&E, immunohistochemical, and TUNEL staining. Results Juglone suppressed T24 and UMUC-3 cell proliferation, enhanced autophagy markers, and induced apoptosis. Network analysis identified 108 shared targets, with AKT1, CASP3, and TP53 as core nodes. Pathway enrichment implicated the PI3K/Akt signalling pathway, supported by molecular docking. Autophagy inhibition reduced juglone-induced apoptosis, confirming autophagic death’s role. Conclusions Juglone triggers BLCA autophagy via PI3K/AKT/mTOR, upregulates apoptotic proteins, and activates caspase 3, promoting apoptosis.https://doi.org/10.1007/s00432-025-06243-5Network pharmacologyJugloneBladder cancerAutophagyPI3K/AKT pathway |
| spellingShingle | Yuanfeng Zhang Enguang Yang Xinyu Zhang Ze Zhang Guoxin Huang Baoyuan Tang Chaohu Chen Longhui Lai Zixu Pei Yonghai Zhang Zhiping Wang Autophagy-related biological targets and network mechanisms of juglone against bladder cancer Journal of Cancer Research and Clinical Oncology Network pharmacology Juglone Bladder cancer Autophagy PI3K/AKT pathway |
| title | Autophagy-related biological targets and network mechanisms of juglone against bladder cancer |
| title_full | Autophagy-related biological targets and network mechanisms of juglone against bladder cancer |
| title_fullStr | Autophagy-related biological targets and network mechanisms of juglone against bladder cancer |
| title_full_unstemmed | Autophagy-related biological targets and network mechanisms of juglone against bladder cancer |
| title_short | Autophagy-related biological targets and network mechanisms of juglone against bladder cancer |
| title_sort | autophagy related biological targets and network mechanisms of juglone against bladder cancer |
| topic | Network pharmacology Juglone Bladder cancer Autophagy PI3K/AKT pathway |
| url | https://doi.org/10.1007/s00432-025-06243-5 |
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