CDK4 and melanoma: Regarding AhR ligands from tryptophan metabolism, we found a similar contradiction: KYN and KYNA, as endogenous AhR ligands, suppressed cyclin D1 and CDK4 protein levels in A375 cells and decreased Rb protein phosphorylation in melanoma cell lines, yet KYNA showed an opposing effect on protein levels and cell cycle regulators in metastatic RPMI7951 cells [151].