Figure 8. Summary for mechanisms of myricetin in the chemoprevention of intestinal tumorigenesis in APC^Min/+ mice.

APC as a canonical tumor suppressor forms a “destruction complex” with Axin/Axin2 and GSK-3β that promotes ubiquitination and proteasomal degradation of β-catenin. Loss of APC function leads to dysfunction of GSK-3β, and results in an accumulation of β-catenin, which translocates to nucleus and engages Tcf/Lef transcription factor complex to activate transcription of a large number of target genes, such as cyclin D1, PCNA, c-myc and CRDBP, etc. Myricetin exerts anti-proliferative, apoptotic and anti-inflammatory activities on the intestinal adenomatous polyps through multiple mechanisms including modulation of GSK-3β and β-catenin signaling pathways, and inhibition of p38 MAPK and Akt/mTOR signaling pathways.