Diosmetin (DS)

Diosmetin is an O-methylated flavone, a chemical compound that can be found in the Caucasian vetch. Diosmetin was metabolized to luteolin via an aromatic demethylation reaction on the B-ring from CYP1A1, CYP1B1 and the hepatic isozyme CYP1A2. CYP1A1 and CYP1A2 also produced additional unidentified metabolites. CYP1B1 showed the lowest apparent KM and CYP1A1 the highest apparent Kcat. Diosmetin was also metabolized to luteolin in estrogen receptor positive breast cell-line (MCF-7 cells) preinduced for 24 h with the potent CYP1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Treatment of MCF-7 cells with TCDD caused bioactivation of diosmetin enhancing its cytotoxicity. Taken together these data suggest that the flavonoid diosmetin is metabolised to the more active molecule luteolin by CYP1 family enzymes.