Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition
Figure 3
Lycopene induces cell-cycle arrest and apoptosis. Growth factors, such as PDGF and IGF, enhance cell survival by protecting cells from apoptosis. Lycopene blocks cell-cycle progression from G1 to S phase, predominantly by reducing the levels of cyc D and E and subsequently inactivating CDK4 and 2 and reducing the phosphorylation of Rb. Furthermore, lycopene increases the levels of the CDK inhibitors p21 and p27 and the tumour suppressor p53 and reduces levels of SKP2 (leaf panel). Lycopene promotes apoptosis by decreasing Bcl-2, and survivin expression, increasing the levels of the proapoptotic proteins Bax, Bad, Bim, and Fas ligand, and activating caspases 8, 9, and 3 (right panel). Lycopene can also block growth factor-mediated antiapoptotic signals by directly inhibiting the binding of growth factors to their receptors or by inhibiting the downstream PI3K-AKT pathway. Lycopene can elicit AKT-induced cell-cycle arrest and apoptosis through the phosphorylation and inactivation of GSK3β, p21, p27, Bad, and caspase 9, as well as the inactivation of p53 via Mdm2.
