Journal Article Epublish
PubMed: 40346358 DOI: 10.1038/s41598-025-96892-w
Bousigonine D from Bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistance.
Sci Rep 15(1):16254
Authors: Kai Shi, Xinyuan Li, Rui Chen, Zhiwei Wang, Benkang Shi, Ke Wang, Yaofeng Zhu
Affiliations
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Cultural West Road, Jinan, 250012, Shandong Province, China.
- Department of Immunology, Shandong Provincial Key Laboratory of Infection and Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, China.
- School 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 Province, Jinan, 250117, Shandong, China.
- Department of Urology, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Qingdao, 266001, Shandong Province, China.
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Cultural West Road, Jinan, 250012, Shandong Province, China.
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.
MeSH
Urinary Bladder, Urinary Bladder Neoplasms, Cells, Growth, Neoplasms, Therapeutics, Apoptosis