Fertility and sterility · 2015
Berberine inhibits the proliferation of human uterine leiomyoma cells.
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Wu Hsiao-Li, Chuang Tung-Yueh, Al-Hendy Ayman, Diamond Michael P, Azziz Ricardo, Chen Yen-Hao
Аннотация
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 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.
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. 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.
CONCLUSION(S): 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.
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 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.
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. 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.
CONCLUSION(S): 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.