Molecular modeling demonstrated that CYP1B1 favored the A ring orientation of apigenin and luteolin to the heme group. The metabolism of hydroxylated flavonoids by cytochrome P450 CYP1 enzymes, notably CYP1A1 and CYP1B1, can enhance their antiproliferative activity in breast cancer cells. The gene discussed is CYP1A1; the disease is breast cancer.