Bousigonine D from Bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistance
Abstract The rising global incidence of bladder cancer and chemotherapy resistance necessitate novel therapies. Plant-derived compounds, owing to their diverse biological activities and favorable safety profiles, are considered promising candidates for cancer treatment. In this study, we investigate...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-96892-w |
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| author | Kai Shi Xinyuan Li Rui Chen Zhiwei Wang Benkang Shi Ke Wang Yaofeng Zhu |
| author_facet | Kai Shi Xinyuan Li Rui Chen Zhiwei Wang Benkang Shi Ke Wang Yaofeng Zhu |
| author_sort | Kai Shi |
| collection | DOAJ |
| description | Abstract The rising global incidence of bladder cancer and chemotherapy resistance necessitate novel therapies. Plant-derived compounds, owing to their diverse biological activities and favorable safety profiles, are considered promising candidates for cancer treatment. In this study, we investigated Bousigonine D, a monoterpene indole alkaloid isolated from the roots of Bousigonia mekongensis, for its potential as a therapeutic agent for bladder cancer. Our results show that Bousigonine D effectively inhibits cell proliferation and clonogenic formation, and induces cell cycle arrest at the G0/G1 phase in murine and human bladder cancer cells. Furthermore, Bousigonine D significantly promotes apoptosis in these cells, surpassing the apoptosis-inducing efficacy of cisplatin. Mechanistically, Bousigonine D enhances the generation of reactive oxygen species, disrupts calcium homeostasis, and impairs mitochondrial function, leading to cytoskeletal collapse and caspase-dependent apoptotic cell death. In vivo, Bousigonine D effectively suppresses tumor growth in an orthotopic MB49 mouse model, and importantly, it retains strong anti-tumor efficacy in cisplatin-resistant bladder cancer. Notably, Bousigonine D exhibits low toxicity in major organs, similar to cisplatin, underscoring its potential as a safe and effective treatment for bladder cancer. This study highlights the promising role of plant-derived compounds in cancer therapy and supports further development of Bousigonine D as a novel therapeutic option for bladder cancer. |
| format | Article |
| id | doaj-art-2210f2192ea74119816d0db5835c2ba6 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-2210f2192ea74119816d0db5835c2ba62025-08-20T02:15:10ZengNature PortfolioScientific Reports2045-23222025-05-0115111310.1038/s41598-025-96892-wBousigonine D from Bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistanceKai Shi0Xinyuan Li1Rui Chen2Zhiwei Wang3Benkang Shi4Ke Wang5Yaofeng Zhu6Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Immunology, Shandong Provincial Key Laboratory of Infection and Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversitySchool of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, National Key Laboratory of Advanced Drug Delivery System, Key Laboratory for Biotechnology Drugs of National Health Commission (Shandong Academy of Medical Sciences), Key Lab for Rare & Uncommon Diseases of Shandong ProvinceDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Urology, The Affiliated Hospital of Qingdao UniversityDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityAbstract The rising global incidence of bladder cancer and chemotherapy resistance necessitate novel therapies. Plant-derived compounds, owing to their diverse biological activities and favorable safety profiles, are considered promising candidates for cancer treatment. In this study, we investigated Bousigonine D, a monoterpene indole alkaloid isolated from the roots of Bousigonia mekongensis, for its potential as a therapeutic agent for bladder cancer. Our results show that Bousigonine D effectively inhibits cell proliferation and clonogenic formation, and induces cell cycle arrest at the G0/G1 phase in murine and human bladder cancer cells. Furthermore, Bousigonine D significantly promotes apoptosis in these cells, surpassing the apoptosis-inducing efficacy of cisplatin. Mechanistically, Bousigonine D enhances the generation of reactive oxygen species, disrupts calcium homeostasis, and impairs mitochondrial function, leading to cytoskeletal collapse and caspase-dependent apoptotic cell death. In vivo, Bousigonine D effectively suppresses tumor growth in an orthotopic MB49 mouse model, and importantly, it retains strong anti-tumor efficacy in cisplatin-resistant bladder cancer. Notably, Bousigonine D exhibits low toxicity in major organs, similar to cisplatin, underscoring its potential as a safe and effective treatment for bladder cancer. This study highlights the promising role of plant-derived compounds in cancer therapy and supports further development of Bousigonine D as a novel therapeutic option for bladder cancer.https://doi.org/10.1038/s41598-025-96892-wBladder cancerBousigonine DApoptosisCisplatin-resistantMitochondrial |
| spellingShingle | Kai Shi Xinyuan Li Rui Chen Zhiwei Wang Benkang Shi Ke Wang Yaofeng Zhu Bousigonine D from Bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistance Scientific Reports Bladder cancer Bousigonine D Apoptosis Cisplatin-resistant Mitochondrial |
| title | Bousigonine D from Bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistance |
| title_full | Bousigonine D from Bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistance |
| title_fullStr | Bousigonine D from Bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistance |
| title_full_unstemmed | Bousigonine D from Bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistance |
| title_short | Bousigonine D from Bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistance |
| title_sort | bousigonine d from bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistance |
| topic | Bladder cancer Bousigonine D Apoptosis Cisplatin-resistant Mitochondrial |
| url | https://doi.org/10.1038/s41598-025-96892-w |
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