Fertility and Sterility 2015-04-01

Berberine inhibits the proliferation of human uterine leiomyoma cells.

Hsiao-Li Wu, Tung-Yueh Chuang, Ayman Al-Hendy, Michael P Diamond, Ricardo Azziz, Yen-Hao Chen

Index: Fertil. Steril. 103(4) , 1098-106, (2015)

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Abstract

To determine whether berberine (BBR), a naturally occurring plant-derived alkaloid, inhibits the proliferation of human uterine leiomyoma (UtLM) cells.Laboratory research.Laboratory.UtLM and normal human uterine smooth muscle (UtSMC) cell lines.Treatment with [1] BBR (10, 20, and 50 μM), [2] BBR (20 and 50 μM) and/or 17β-estradiol (E2; 10 and 100 nM), and [3] BBR (20 and 50 μM) and/or progesterone (P4; 10 and 100 nM) for 24 or 72 hours.Cell proliferation, cell cycle, apoptosis, and related genes expression were determined.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. E2- and P4-induced UtLM cell proliferation was blocked by BBR treatment. In marked contrast, even the highest concentration of BBR (50 μM) did not influence cell proliferation in UtSMC cells.BBR selectively inhibits cellular proliferation and blocks E2- and P4-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.Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.