Dietary natural flavonoids treating cancer by targeting aryl hydrocarbon receptor

The role of aryl hydrocarbon receptor (AhR) as a ligand-activated transcription factor in the field of cancer has gradually been unveiled. A strong body of evidence indicated that AhR is implicated in cell proliferation and apoptosis, immune metabolism and other processes, which further affected tumor growth, survival, migration, and invasion. Therefore, AhR targeted therapy may become a new method for cancer treatment and provide a new direction for clinical tumor treatment. Astonishingly, the largest source of exposure of animals and humans to AhR ligands (synthetic and natural) comes from the diet. Myriad studies have described that various natural dietary chemicals can directly activate and/or inhibit the AhR signaling pathway. Of note, numerous natural products contribute to AhR active, of which dietary flavonoids are the largest class of natural AhR ligands. As interest in AhR and its ligands increases, it seems sensible to summarize current research on these ligands. In this review, we highlight the role of AhR in tumorigenesis and focus on the double effect of AhR in cancer therapy. We explored the molecular mechanism of AhR ligands on cancer through a few AhR agonists/antagonists currently in clinical practice. Ultimately, we summarize and highlight the latest progression of dietary flavonoids as AhR ligands in cancer inhibition, including the limitations and deficiencies of it in clinical research. This review will offer a comprehensive understanding of AhR and its dietary ligands which may dramatically pave the way for targeted cancer treatment.