Effect of drospirenone on proliferation of human benign and cancerous epithelial breast cells

Abstract

Background: Proliferation of human breast epithelial cells is regulated by sex hormones. Epidemiological studies indicate that progestogen addition to estrogen therapy can increase breast cancer risk. However, it remains unclear if all progestogens react in a similar manner. Here, the new progestogen drospirenone (DRSP) was compared to progesterone and other synthetic progestins.

Design and methods: Human benign epithelial breast cells (HMECs) were incubated for 7 days with DRSP, progesterone (P), medroxyprogesterone acetate (MPA) and levonorgestrel (LNG) in the presence of a growth factor mixture (GF). HCC1500 and T-47D cells (human estrogen and progesterone receptor-positive primary breast cancer cells) were also incubated with the progestogens, but in the presence of estradiol (E2). The proliferation rate was measured by the MTT assay.

Results: DRSP and P elicited a similar significant inhibition of proliferation of HMECs in combination with GFs. LNG and MPA had no effect. DRSP, P, MPA and LNG were able to significantly inhibit the proliferation of HCC1500 and T-47D cells in combination with E2. No significant difference between the progestogens was observed in HCC1500 cells, whereas in T-47D cells both DRSP and P were significantly more effective at 10 μM than LNG and MPA.

Conclusion: Because different results were found in the same experimental model, it appears that progestogens do not react similarly on the proliferation of human breast epithelial cells. However, for assessment of breast cancer risk different models should be used, because various mechanism(s) might be involved. It is also important to use benign as well as cancerous cell lines. The choice of progestogen could be of significance in terms of breast cancer risk under hormone therapy.