Background: Colon cancer is one of the most prevalent gastrointestinal malignancies worldwide, with high mortality and limited therapeutic options. Puerarin, a flavonoid compound derived from Pueraria lobata, has shown anticancer potential, but its molecular mechanisms against colon cancer remain unclear. Methods and Results: In this study, human colon cancer Caco-2 cells were treated with various concentrations of puerarin. Cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and apoptosis were evaluated using CCK-8, wound healing, Transwell, immunofluorescence, flow cytometry, and Western blot assays. Puerarin significantly inhibited Caco-2 cell proliferation in a dose- and time-dependent manner. It suppressed migration and invasion by increasing E-cadherin and reducing Vimentin expression. Apoptosis was induced via upregulation of BAX and downregulation of Bcl-2. Network pharmacology and KEGG analysis suggested PI3K/AKT signaling as a core regulatory pathway. Western blotting confirmed that puerarin reduced phosphorylation of PI3K and AKT. PI3K activator 740 Y-P promoted EMT and inhibited apoptosis, whereas puerarin and the PI3K inhibitor LY294002 reversed these effects. Conclusions: Puerarin exerts significant antitumor effects on Caco-2 colon cancer cells by inhibiting proliferation, migration, and EMT, while promoting apoptosis. These effects are mediated primarily through suppression of the PI3K/AKT signaling pathway. This study provides a theoretical basis for the use of puerarin as a natural therapeutic agent in colon cancer treatment.
Chen et al. (2025) studied this question.