Berberine inhibits the proliferation of human uterine leiomyoma cells

Objective: To determine whether berberine (BBR), a naturally occurring plant-derived alkaloid, inhibits the proliferation of human uterine leiomyoma (UtLM) cells. Design: Laboratory research. Setting: Laboratory. Patient(s): UtLM and normal human uterine smooth muscle (UtSMC) cell lines. Intervention(s): Treatment with [1] BBR (10, 20, and 50 mu M), [2] BBR (20 and 50 mu M) and/or 17 beta-estradiol (E-2; 10 and 100 nM), and [3] BBR (20 and 50 mu M) and/or progesterone (P-4; 10 and 100 nM) for 24 or 72 hours. Main Outcome Measure(s): Cell proliferation, cell cycle, apoptosis, and related genes expression were determined. Result(s): BBR inhibited UtLM cell proliferation by inducing G2/M cell cycle arrest and apoptosis. Cell cycle G2/M phase-related genes were altered by BBR treatment: the expression of cyclin A1, cyclin B1, and Cdk1 were down-regulated, while Cdk4, p21, and p53 were up-regulated. BBR-treated cells stained positively for annexin V and manifested increased BAX expression. E-2- and P-4-induced UtLM cell proliferation was blocked by BBR treatment. In marked contrast, even the highest concentration of BBR (50 mM) did not influence cell proliferation in UtSMC cells. Conclusion(s): BBR selectively inhibits cellular proliferation and blocks E-2- and P-4-induced cell proliferation in UtLM but not in normal UtSMC cells. In addition, BBR did not demonstrate cytotoxicity effects in normal human UtSMCs. Our results suggest BBR could be a potential therapeutic agent for the treatment of uterine leiomyoma. (C) 2015 by American Society for Reproductive Medicine.