Shi Kai, Li Xinyuan, Chen Rui, Wang Zhiwei, Shi Benkang, Wang Ke, Zhu Yaofeng
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.
Sci Rep. 2025 May 9;15(1):16254. doi: 10.1038/s41598-025-96892-w.
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.
全球膀胱癌发病率的上升以及化疗耐药性使得新型疗法成为必要。植物来源的化合物因其多样的生物活性和良好的安全性，被认为是癌症治疗的有前景的候选物。在本研究中，我们研究了从湄公河布西戈尼亚根部分离出的单萜吲哚生物碱布西戈宁D作为膀胱癌治疗剂的潜力。我们的结果表明，布西戈宁D有效抑制细胞增殖和克隆形成，并在小鼠和人膀胱癌细胞中诱导细胞周期停滞在G0/G1期。此外，布西戈宁D显著促进这些细胞的凋亡，超过顺铂的凋亡诱导效力。从机制上讲，布西戈宁D增强活性氧的产生，破坏钙稳态，并损害线粒体功能，导致细胞骨架塌陷和半胱天冬酶依赖性凋亡细胞死亡。在体内，布西戈宁D在原位MB49小鼠模型中有效抑制肿瘤生长，重要的是，它在顺铂耐药的膀胱癌中保留强大的抗肿瘤效力。值得注意的是，布西戈宁D在主要器官中表现出低毒性，与顺铂相似，突出了其作为膀胱癌安全有效治疗方法的潜力。这项研究突出了植物来源的化合物在癌症治疗中的有前景的作用，并支持将布西戈宁D进一步开发为膀胱癌的新型治疗选择。
