Polydatin as a Multifunctional Anticancer Agent: Cellular Mechanisms, Therapeutic Potential and Future Clinical...

Cancer remains one of the leading causes of death worldwide, with conventional treatments often facing limitations such as toxicity, drug resistance, and reduced effectiveness over time. Polydatin (PD), a natural glycosylated derivative of resveratrol, has emerged as a promising therapeutic compound due to its ability to induce apoptosis, regulate the cell cycle, modulate oxidative stress, and inhibit angiogenesis. Additionally, PD plays a key role in shaping the tumor microenvironment and enhancing immune responses, making it a strong candidate for use alongside chemotherapy and radiotherapy. This review examines PD's pharmacological potential, highlighting its anticancer mechanisms, therapeutic combinations, and clinical relevance. A systematic literature search was conducted using PubMed, Scopus and Web of Science to analyze preclinical and clinical studies published between 2010 and 2024. Findings suggest that PD enhances chemotherapy efficacy, increases tumor sensitivity to radiotherapy, and reduces drug resistance by targeting critical signaling pathways, including phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK). Beyond cancer treatment, PD has demonstrated cardioprotective, neuroprotective, and hepatoprotective properties, further supporting its clinical potential. Despite encouraging preclinical evidence, clinical studies on PD remain limited, emphasizing the need for further investigations into its pharmacokinetics, bioavailability, and safety. Moving forward, research should focus on improving drug delivery systems, conducting rigorous clinical trials, and exploring PD's role in precision medicine to maximize its therapeutic impact in oncology and beyond.