CUL3 and cancer: Because the mitogen-activated protein kinase (MAPK) cascade has been shown to play an important role in the intracellular signaling of hypoxic cancer cells [34] and to regulate the Nrf2 signaling pathway [33], we investigated whether QC regulates MAPKs, as well as Keap1 and Cul3, in CRC cells under either normoxic or hypoxic conditions.