Preferential Induction of CYP1A1 over CYP1B1 in Human Breast Cancer MCF-7 Cells after Exposure to Berberine

Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens mightbe attributed to DNA modification caused by derivatives formed during metabolism. 17β-estradiol (E2), the mainsteroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol(2-OH E2) and 4-hydroxyestradiol (4-OH E2) through the action of cytochrome P450 (CYP) 1A1 and 1B1,respectively. Previous reports suggested that 2-OH E2 has putative protective effects, while 4-OH E2 is genotoxicand has potent carcinogenic activity. Thus, the ratio of 2-OH E2/4-OH E2 is a critical determinant of the toxicityof E2 in mammary cells. In the present study, we investigated the effects of berberine on the expression profileof the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatmentproduced significant induction of both forms at the level of mRNA expression, but with increased doses produced16~ to 52~fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramaticallyincreased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion,we present the first report to show that berberine may provide protection against breast cancer by altering theratio of CYP1A1/CYP1B1, could redirect E2 metabolism in a more protective pathway in breast cancer MCF-7cells.