Nobiletin in cancer therapy: Emerging insights into multi-target mechanisms, overcoming drug resistance and therapeutic translation (Review).

Nobiletin, a polymethoxyflavone derived from Citrus peels, has emerged as a promising multi-target anticancer agent. The present review consolidates recent advances elucidating the efficacy of nobiletin in suppressing tumor growth across diverse cancer types, including breast, colon, lung and gastric cancer. Mechanisms for inducing cell cycle arrest and apoptosis, inhibiting metastasis and angiogenesis, and modulating key oncogenic pathways, such as phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, mitogen-activated protein kinase and nuclear factor-κB are discussed. Crucially, the present review highlights the role of nobiletin in reversing chemoresistance and its synergistic potential with conventional therapeutics. Despite challenges in bioavailability, novel delivery strategies are paving the way for its clinical application. By reviewing current evidence, the present review underscores the notable potential of nobiletin as an integrative agent in oncology, offering a comprehensive perspective on its therapeutic prospects.