Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition
Lycopene inhibits theWnt/β-catenin pathway. In the absence of Wnt, a multiprotein complex that includes axin, APC, and GSK3β destabilises β-catenin. β-catenin is phosphorylated by GSK3β and is subsequently degraded by the proteasome. Binding of Wnt to its cell surface receptors Fzd and Lrp 5/6 inhibits the phosphorylation of β-catenin by GSK3β, allowing β-catenin to accumulate within the cytosol. β-catenin then translocates into the nucleus, where it binds and activates LEF/TCF and induces gene expression. Lycopene increases the expression of E-cadherin, nm23-H1, and TIMP2, as well as the activity of GSK3β. Furthermore, it decreases the levels of MMPs 2, 7, and 9, uPA, and β-catenin. Lycopene also induces its antimetastatic effects through the inactivation of transcription factors (NF-κB, AP-1, SP-1, and LEF/TCF).
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