Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

Figure 1

A possible mechanism of Nrf2 regulation by lycopene. Under homeostatic conditions, Nrf2 is retained within the cytoplasm by the Keap1 protein. Upon activation of upstream protein kinases (MAPKs, PI3K, PKC, and ERK) and/or direct effects on Keap1, Nrf2 is released from Keap1 and translocated into the nucleus, where Nrf2 associates with small Maf proteins and binds to AREs. Lycopene induces the nuclear translocation of Nrf2. One possible mechanism involves the direct interaction of lycopene with the cysteine residues of Keap1, which triggers the release of Nrf2 from the complex. Lycopene-generated metabolites can activate a wide variety of kinases, which can also induce the release and nuclear translocation of Nrf2.