Abstract
BACKGROUND: Prostate cancer (PCa) is one of the most prevalent malignancies in men, often progressing to castration-resistant forms and resisting conventional therapies. Curcumin, a polyphenol from Curcuma longa, has emerged as a potent anti-cancer agent by modulating several molecular pathways. OBJECTIVE: This systematic review seeks to synthesize current preclinical evidence on the molecular mechanisms underlying curcumin's effects in PCa and to evaluate nanoformulation strategies developed to enhance its pharmacokinetics and therapeutic efficacy. METHODS: A comprehensive search of five major databases up to March 1, 2025 identified 22 eligible studies on curcumin and PCa. Data on molecular pathways, therapeutic outcomes, and delivery systems were extracted and assessed using ToxRTool and SYRCLE guidelines. RESULTS: Curcumin modulated key pathways including PI3K/Akt/mTOR (8 studies), NF-κB (7), AR signaling (6), and apoptosis-related regulators (13). Therapeutic outcomes included apoptosis, necroptosis, cell cycle arrest, and suppression of migration and angiogenesis. Nanoformulations (e.g., Theracurmin®, PLGA-curcumin) demonstrated improved bioavailability and tumor-targeted delivery. Synergistic combinations with docetaxel, quercetin, or phototherapy enhanced its anti-cancer effects. CONCLUSION: Curcumin exerts multi-targeted anticancer effects in PCa models, but clinical translation is hindered by poor bioavailability. Advanced nanoformulations and rational combination therapies offer promising strategies to overcome these limitations. Clinical trials evaluating optimized curcumin delivery systems in well-defined PCa populations are strongly recommended.