Puerarin as a multifaceted anticancer agent: Mechanisms, targets, and therapeutic potential across multiple cancers.

Puerarin (Pue), a key isoflavone from Pueraria lobata, has been traditionally used in Chinese medicine for cardiovascular, cerebrovascular, neurodegenerative, metabolic, and hepatic diseases. Recent studies indicate its anticancer potential across various malignancies. This review explores the current literature on Pue's anticancer activities, mechanisms of action, and molecular targets. Preclinical in vitro and in vivo studies suggest Pue's effectiveness; however, challenges including standardization, selectivity, safety, and delivery hinder clinical translation. Specifically, dose optimization and rigorous standardization are needed to fully elucidate Pue's mechanisms, particularly in hormone-dependent cancers. The development of advanced drug delivery systems, such as nanosuspensions, nanoemulsions, and nanoparticles, is essential to improve Pue's poor water solubility and stability, and to enhance targeted delivery. Studies have shown that Pue can inhibit cancer cell proliferation, induce apoptosis, and suppress metastasis in various cancer cell lines, including breast, colon, lung, and ovarian cancers. Pue's anticancer mechanisms involve modulating multiple signaling pathways, including nuclear factor-κB (NF-κB), extracellular signal-regulated kinase (ERK), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), and Wnt signaling (Wnt), and targeting key molecules such as Caspases, Bcl-2-associated X protein (BAX), B-cell lymphoma-2 (BCL-2), matrix metalloproteinases (MMPs), and dual-specificity phosphatase 1 (DUSP1). Pue has also been found to enhance the efficacy of conventional chemotherapeutic agents such as cisplatin and oxaliplatin, and to overcome drug resistance. Overall, Pue shows promise as a multifaceted anticancer agent, which merits further investigation. This review provides a comprehensive overview of Pue's anticancer effects, emphasizing its potential to guide future cancer treatment strategies.