Unveiling the potential of Urolithin A in Cancer Therapy: Mechanistic Insights to Future Perspectives of Nanomedicine.

Abstract

Cancer remains a leading global health challenge, with high mortality rates persisting despite significant advancements in therapeutic interventions. Major obstacles, including systemic toxicity, therapy resistance, metastasis, and relapses, emphasize the urgent need for safer, more effective, and readily accessible treatment strategies. Among emerging alternatives, natural bioactive compounds have gained considerable attention because of their diverse therapeutic potential and lower toxicity profiles. Urolithin A (UA), a metabolite derived from ellagic acid through gut microbiota metabolism, has emerged as a compelling anticancer agent. UA has multiple mechanisms of action, including the regulation of autophagy, enhancement of mitochondrial function, and inhibition of tumor progression and metastatic pathways. Additionally, its chemo-, immuno-, and radio-sensitization properties further increase its therapeutic advantages. Nanotechnology-driven approaches, such as nanoparticle formulations, lipids, and powder formulations, have successfully increased the solubility, stability, bioavailability, precise targeted delivery to cancer tissues, and overall therapeutic benefits of these materials. This review comprehensively explores the anticancer mechanisms of UA, its modulatory role, and advances in nanoformulation strategies, highlighting its potential as a next-generation therapeutic agent for improved cancer treatment and prevention.