Bousigonine D from Bousigonia mekongensis inhibits bladder cancer growth and overcomes cisplatin resistance.

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.