Dietary flavones and flavonones display differential effects on aromatase (CYP19) transcription in the breast cancer cells MCF-7

Abstract

Aromatase or cytochrome P450 (CYP19) enzyme catalyzes the rate-determining reaction in estrogen synthesis. Inhibiting aromatase is a major strategy in treating breast cancer patients. However, suppression on the transcriptional activity may be equally important in controlling aromatase. Dietary flavones and flavonones have been previously demonstrated to be the most potent aromatase-inhibitory flavonoids. In the present study we examined their effects on the transcription regulation of CYP19 in MCF-7 cells. Real-time PCR results indicated that luteolin suppressed CYP19 mRNA expression while hesperetin increased it. Reporter gene assays were employed to look into the transactivity of CYP19 driven by promoters I.3 and II, and the result was consistent with the observation in mRNA expression. Further investigation using truncation reporter gene and electrophoretic mobility shift assays suggested that luteolin and hesperetin differentially influenced AP-1- and C/EBP-binding on the CYP19 promoter. Western blot analysis indicated that signaling transduction pathways involving JNK and ERK could be the underlying mechanisms for their actions. The present study showed that dietary flavones and flavonones might differentially regulate aromatase transcription in breast cells in addition to the inhibition at the enzyme level.