Figure 3.

Summary of the four focus areas to develop quercetin as a chemo-preventative or therapeutic agent. In melanoma prevention scenarios (left), quercetin would be ingested through food sources and the concentration in normal melanocytes would be relatively low. Antioxidant activities and signaling pathways leading to the induction of cytoprotective proteins would dominate. Evidence suggests that quercetin may impart transcriptionally permissive epigenetic modifications within key tumor suppressor genes, including p16, which could confer resistance to oncogenesis. Induction of miRNAs could also aid in cancer prevention. In therapeutic protocols (right), quercetin would be delivered alone or in combination with anti-melanoma pharmaceuticals. Quercetin and additional compounds could be delivered through nanoparticles targeted to melanoma cells, or in an untargeted regimen. Pro-oxidant effects would be desired, and induction of wild-type p53 and other apoptotic factors would aid in therapy. Epigenetic mechanisms would likely be more prominent in prevention (blue line), but miRNAs have been shown to play a significant role in circumventing drug resistance.