Taxifolin Inhibits Melanoma Proliferation/migration Impeding USP18/ Rac1/JNK/β-catenin Oncogenic Signaling

Background: Metastatic melanoma is a fatal cancer. Despite the advances in targeted therapy and immunotherapy for patients with melanoma, drug resistance and low response rates pose a considerable challenge. Taxifolin is a multifunctional natural compound with emerging antitumor potentials. However, its utility in melanoma treatment remains unclear.Purpose: The study aimed to investigate the effect of purified Taxifolin from Larix olgensis roots (Changbai Mountain, China) on melanoma and explore the underlying mechanism.Methods: Purified Taxifolin from Larix olgensis roots was evaluated for its antimelanoma effects in vitro and in vivo settings. RNA-seq analysis was performed to explore the underlying mechanism.Results: Purified Taxifolin (> 99 %) from Larix olgensis roots inhibited the proliferation and migration of B16F10 melanoma cells at 200 and 400 mu M, and of A375 cells at 100 and 200 mu M. Taxifolin administered at 60 mg/kg suppressed tumor growth and metastasis in mouse models without causing significant toxicity. Taxifolin modulated USP18/Rac1/JNK/beta-catenin axis to exert its antitumor effect. Conclusion: These findings indicate that Taxifolin derived from Larix olgensis roots may be a promising antimelanoma therapy.