TI - FZC18 reduces tumor cell growth . AB - In CRC and HCC cell lines , FZC18 decreases the protein levels of total and non-PHOSphorylated beta-catenin and downstream targets , such as cyclin D1 and c-myc . These findings are associated with ~60% to 70% reduction of tumor cell growth and ~25% induction of cell death . These data are consistent with the fact that SFRP1 , SFRP2 and SFRP5 suppress Wnt -dependent transcription by 60% , decrease c-myc mRNA expression , inhibit in vitro tumor growth and induce cell death in CRC cells carrying oncogenic mutations of beta-catenin [15] . Similarly , SFRP1 sensitizes breast cancer cells to proapoptotic stimuli [29] and SFRP3 suppresses tumor growth and cell invasion in prostate cancer cells [30] . Wnt-induced beta-catenin stabilization is an important survival signal which regulates homeostasis [31] and increases the threshold for contact inhibition and anchorage -independent cell growth [32] . As a result , reduction in tumor cell growth can be achieved by either extracellular quenching of Wnts with monoclonal antibodies [33] , [34] , beta-catenin knockdown [35] or restoring normal APC [36] . FZC18 turns off c-myc in CRC cells , which may explain the induction of cell death . Indeed , Wnt signaling disables the checkpoint of c-myc-induced apoptosis in tumor cells [37] , thus enhancing its prooncogenic effects [38] . Although c-myc is a target of beta-catenin in CRCs [39] , its link with beta-catenin in HCCs remains controversial [40] , [41] . In addition , FZC18 turns off cyclin D1 in CRC and HCC cancer cell lines . Cyclin D1 is a downstream effector of beta-catenin , promoting S-phase entry and tumor growth [42] and is frequently upregulated in HCCs [41] . The common theme in these approaches is the inhibition of the Wnt/beta-catenin pathway at different levels , providing a rationale for therapeutic intervention [36] . Particularly , inhibiting Wnt-FZ interaction at the cell surface was recently indicated as a viable strategy for anti-cancer treatment [43] .