Exploring the Therapeutic Potential of Nobiletin in Nonsmall Cell Lung Cancer.

Nonsmall cell lung cancer (NSCLC) is one of the most prevalent cancers and leading causes of cancer-related mortality worldwide. Despite advancements in medical treatment, current therapeutic strategies are often hindered by late-stage diagnosis, high recurrence rates and resistance to therapies. These challenges highlight the urgent need for novel, less toxic and more effective treatment options. Phytoceuticals, bioactive plant-derived compounds, have gained increasing attention for their potential to complement or enhance conventional cancer therapies. Among these, nobiletin, a polymethoxylated flavonoid found in citrus peels, has promising anti-inflammatory, antioxidant and anticancer properties. This review explores the therapeutic potential of nobiletin in NSCLC, focusing on its ability to modulate key cancer hallmarks such as uncontrolled proliferation, metastasis, immune evasion and multidrug resistance. Preclinical studies suggest that nobiletin inhibits tumour growth, enhances chemosensitivity and suppresses metastasis through multiple pathways. However, its clinical application is currently limited by poor bioavailability, prompting the need for innovative delivery strategies. Therefore, this review also discusses emerging approaches to improve nobiletin's biological activity, supporting further investigations into its role in NSCLC therapy.