LF3 does not cause cell death or interfere with cadherin-mediated cell-cell adhesion. The self-renewal capacity of cancer stem cells is blocked by LF3 in concentration-dependent manners, as examined by sphere formation of colon and head and neck cancer stem cells under nonadherent conditions. LF3 inhibits Wnt/β-catenin signaling, but does not interfere with E-cadherin/β-catenin-mediated cell-cell adhesion. LF3 blocks the expression of a series of Wnt target genes in Wnt-addicted colon cancer cells. It inhibits proliferation of Wnt-addicted colon cancer cells through induction of cell-cycle arrest and also inhibits self-renewal capacity of CSCs.
In vivo
LF3 reduces tumor growth and induces differentiation in a mouse xenograft model of colon cancer while exhibiting no significant toxicity for mice and does not disturb the normal histology of the gut of mice.
