Quercetin unveiled: Targeting NF-κB and p53 pathways to combat Uveal Melanoma

Abstract

Uveal melanoma is the most frequently diagnosed primary intraocular tumour in adults, with metastasis occurring in nearly 50% of adults, primarily to the liver and the limited treatment options due to its chemoresistance. NF-κB and p53 are key transcription factors regulating cell survival, growth, and apoptosis. Quercetin (QUE), a naturally occurring flavonol, exhibits anti-cancer properties by activating p53 and inhibiting NF-κB signalling through suppression of IκB kinases, therefore preventing translocation to the nucleus. In this study, QUE significantly reduced uveal melanoma cell viability in a concentration-dependent manner (1–100 µM), as demonstrated by MTT assay and Bürker chamber analysis. Fluorescence imaging revealed a decrease in nuclear NF-κB intensity with a corresponding increase in the cytoplasm, while nuclear p53 intensity increased with QUE treatment (10 µM) compared to untreated, indicating altered subcellular localisation of both transcription factors. These results support the potential of QUE as a well-tolerated and effective adjunct in combination therapy for uveal melanoma.