Koumine exerts its anti-colorectal cancer effects by disrupting the interaction between HSP90 and CDC37, thereby downregulating downstream signaling pathways

HaiLing Lin¹YuXuan Bao¹MaoBai Liu¹ShuMing Zhang¹DanYang Zhou^2,3*Wancai Que^1*

• ¹Fujian Medical University Union Hospital, Fuzhou, China
• ²Nanjing First Hospital, Nanjing, China
• ³Nanjing Medical University, Nanjing, China

Koumine, the main active alkaloid component of the traditional Chinese herb Gelsemium, has been reported in literature for its cytotoxic effects on various cancer cells. However, its specific mechanisms and efficacy against colorectal cancer remained unclear. In this study, employing network pharmacology, we analyzed the potential targets of koumine in colorectal cancer and the enriched signaling pathways associated with these targets. Our findings indicate that koumine may target crucial signaling pathways essential for tumor development. Furthermore, molecular docking simulations suggested potential interactions between koumine and proteins such as HSP90. Cellular functional assays validated that koumine treatment inhibits cell proliferation and colony formation, induces apoptosis, slows wound healing, and reduces cell invasion through Transwell chambers, confirming its anticancer properties. Initial CETSA experiments provided preliminary evidence of the interaction between HSP90 and koumine, while subsequent Western blot assays suggested that koumine may disrupt the HSP90-CDC37 interaction, thereby suppressing the expression and activation of downstream proteins like CDK4 and CDK6, impairing tumor cell function. These experimental results collectively underscore the anticancer efficacy and molecular mechanisms of koumine against colorectal cancer, offering theoretical support for its potential clinical applications.