Nobiletin suppresses nasopharyngeal carcinoma by regulating the KEAP1/NRF2/ARE pathway

• Nobiletin (NOB) suppresses nasopharyngeal carcinoma (NPC) by activating KEAP1, leading to NRF2 degradation and disruption of the NRF2/ARE pathway. • NOB inhibits migration and invasion of NPC cells (CNE-2 and 5-8F) in a dose- and time-dependent manner. • Mechanistically, NOB increases intracellular ROS levels and enhances antitumor immunity by downregulating ARE-driven antioxidant genes. • KEAP1 is identified as a promising therapeutic target for NPC, and NOB may serve as a natural sensitizer in chemotherapy.