Molecular Mechanisms of Anticancer Activity in Codonopsis pilosula Bioactive Compounds and Their Therapeutic Targets

The present study elucidates the molecular mechanisms underlying the anticancer effects of Codonopsis pilosula bioactive compounds. Polysaccharides exert immunomodulatory effects by activating macrophages and NK cells through TLR4/NF-κB signaling, while inhibiting angiogenesis via VEGF/VEGFR2 and TGF-β/Smad pathway suppression. Saponins like lobetyolin disrupt glutamine metabolism by downregulating ASCT2 expression through c-Myc inhibition, inducing mitochondrial apoptosis via ROS/JNK activation. Polyacetylenes, particularly codonolactone, suppress EMT by blocking TGF-β-induced Smad2/3 phosphorylation and Runx2 nuclear translocation. Phenolic compounds such as luteolin induce G2/M arrest through CDK1/cyclin B1 modulation and inhibit migration via PI3K/AKT/ESR1 axis regulation. The study provides a comprehensive molecular basis for C. pilosula's anticancer potential, supporting its development as a multi-targeted therapeutic agent. Future research should focus on clinical translation of these mechanistically defined bioactive compounds.