Kaempferol suppresses prostate cancer metastasis and tumor angiogenesis via disrupting the LIMK1/Cofilin pathway.

Tumor neovascularization promotes prostate cancer (PCa) progression, positioning anti-angiogenic therapy as a promising therapeutic strategy. Secondary metabolites from edible plants, particularly kaempferol, have demonstrated efficacy in suppressing PCa metastasis, yet its underlying mechanisms remain elusive. CCK-8 and colony formation assays were implemented to assess the cytotoxicity of kaempferol. Flow cytometry was executed to detect cell apoptosis and cell cycle arrest. The expression of molecules related to angiogenesis and cell cycle regulation was detected by immunofluorescence and Western blotting. A nude mouse prostate cancer xenograft model was established, with in vivo validation via H&E staining, ELISA, immunohistochemistry, and Western blotting assay. Kaempferol exerted pleiotropic anti-tumor effects on prostate cancer cells, including inhibiting the proliferation, inducing apoptosis and causing cell cycle arrest. Additionally, kaempferol decreased the expression of VEGFA, CDK4, and CDK6. Mechanistically, kaempferol disrupted the LIMK1/Cofilin signaling pathway, thereby inhibiting the angiogenic ability of tumor cells and suppressing the tumorigenic ability. In vivo xenograft experiments further confirmed kaempferol's efficacy in suppressing tumor growth. These findings support potential of kaempferol as a therapeutic agent for metastatic PCa. The identified LIMK1/Cofilin-dependent mechanism underscores the anti-metastasis effect of kaempferol and highlights LIMK1 as a therapeutic target, providing a rationale for further investigating kaempferol in prostate cancer progression.