A model of TQ’s effect on colon cancer cells. In untreated colorectal cells GSK-3β is phosphorylated on Ser9 by various pathways (Ras-Raf-MEK, PI3K-AKT1, WNT), and thereby inactivated. This allows accumulation of β-catenin in the cytoplasm, its nuclear translocation and activation of Tcf/LEF-1. Thymoquinone (TQ) treatment reduces GSK-3β Ser9 phosphorylation (downstream of Ras, Raf, MEK) leading to a relocalization of β-catenin to the membrane (green arrows) and reduction of nuclear c-myc (likely via phosphorylation, ubiquitination and subsequent degradation; blue arrow; ref. 37).