LYCOPENE INDUCES APOPTOSIS BY INHIBITING NUCLEAR TRANSLOCATION OF β-CATENIN IN GASTRIC CANCER CELLS

Reactive oxygen species (ROS) promote the development and progression of cancer by their effects on several signaling pathways. Lycopene, a major carotenoid natural product, is known to display antioxidant activity and to induce apoptosis of cancer cells. The aim of the present study was to investigate the mechanism by which lycopene induces apoptosis of the human gastric cancer AGS cells. In the present study, we showed that lycopene reduces the viability of AGS cells by inducing DNA fragmentation and increasing the Bax/Bcl-2 ratio. To determine the mechanistic basis for these effects, studies were conducted to assess the effects of this carotenoid on activation and nuclear translocation of beta-catenin, and the expression of beta-catenin target genes in AGS cells. The results showed that lycopene reduces the levels of ROS. It also inhibits activation of beta-catenin signaling by changing the Wnt/beta-catenin multi-protein complex such as a reduction in phosphorylation of glycogen synthase kinase 3 beta [GSK3 beta] and an increase in adenomatous polyposis coli [APC] and beta-transducin repeats-containing proteins [beta-TrCP]). It suppresses nuclear translocation of beta-catenin and the expression of the beta-catenin target survival genes c-myc and cyclin D1. Lycopene induces apoptosis by reducing ROS levels and suppressing beta-catenin-c-myc/cyclin D1 axis. Thus, lycopene induces apoptosis of gastric cancer cells by disrupting nuclear translocation of beta-catenin and expression of key cell survival genes.