Nomegestrol acetate is an anti-aromatase agent in human MCF-7aro breast cancer cells.

Abstract

The progestogen nomegestrol acetate (NOMAC), a 17α-hydroxy-nor-progesterone derivative (LUTENYL®) is largely used as an oral contraceptive and to treat menopausal complaints. In previous studies, we demonstrated that NOMAC is an anti-sulfatase agent in MCF-7 and T-47D breast cancer cells. In this study, we explore the effect of NOMAC on aromatase activity in a stable aromatase-expressing human breast cancer cell line: MCF-7aro. Cells were incubated with physiological concentrations of androgen substrates [3H]-testosterone or [3H]-androstenedione (5×10-9mol/L) alone, or in the presence of NOMAC (5×10-5mol/L-5×10-8mol/L) for 24h at 37°C. [3H]-Estradiol (E2), [3H]-estrone (E1), [3H]-testosterone and [3H]-androstenedione were characterized by thin layer chromatography and quantified using the corresponding standard. Aromatase activity levels are high in MCF-7aro cells because the [3H]-E2 concentration after incubation of [3H]-testosterone was 5.8±0.31pmol/mg DNA in non-treated cells. At concentrations of 5×10-5mol/L, 5×10-6mol/L and 5×10-7mol/L NOMAC significantly inhibits this conversion by 49.7%, 29.9% and 18.1%, respectively. After [3H]-androstenedione incubation, similar inhibition levels were observed with NOMAC for [3H]-E1 formation; whereas, inhibition of [3H]-E2 production, which implicates 17β-hydroxysteroid dehydrogenase activity in this pathway, is greater because NOMAC also inhibits this enzyme. The MCF-7aro cell line shows high aromatase activity and NOMAC can act as an anti-aromatase agent by inhibiting this activity. This is an important new effect of this progestogen. Because NOMAC can also inhibit sulfatase activity in breast cancer cells, we suggest that this dual effect of NOMAC has attractive possibilities for clinical trials.