Berberine inhibits the proliferation of human uterine leiomyoma cells

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 mM) 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.

Original languageEnglish (US)
Pages (from-to)1098-1106
Number of pages9
JournalFertility and Sterility
Volume103
Issue number4
DOIs
StateE-pub ahead of print - Feb 14 2015

Fingerprint

Berberine
Leiomyoma
Cell Proliferation
Myometrium
Smooth Muscle Myocytes
Cyclin A1
Cell Cycle
G2 Phase Cell Cycle Checkpoints
Apoptosis
Cyclin B1
Therapeutics
G2 Phase
Annexin A5
Alkaloids
Cell Division
Progesterone
Estradiol

Keywords

  • Anti-tumorigenic
  • Antineoplastic
  • Berberine
  • Fibroids
  • Leiomyomas
  • Treatment
  • Uterus

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Berberine inhibits the proliferation of human uterine leiomyoma cells. / Wu, Hsiao Li; Chuang, Tung Yueh; Al-Hendy, Ayman; Diamond, Michael Peter; Azziz, Ricardo; Chen, Yen-Hao.

In: Fertility and Sterility, Vol. 103, No. 4, 14.02.2015, p. 1098-1106.

Research output: Contribution to journalArticle

Wu, Hsiao Li ; Chuang, Tung Yueh ; Al-Hendy, Ayman ; Diamond, Michael Peter ; Azziz, Ricardo ; Chen, Yen-Hao. / Berberine inhibits the proliferation of human uterine leiomyoma cells. In: Fertility and Sterility. 2015 ; Vol. 103, No. 4. pp. 1098-1106.
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abstract = "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 mM) 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.",
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AU - Wu, Hsiao Li

AU - Chuang, Tung Yueh

AU - Al-Hendy, Ayman

AU - Diamond, Michael Peter

AU - Azziz, Ricardo

AU - Chen, Yen-Hao

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N2 - 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 mM) 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.

AB - 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 mM) 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.

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KW - Fibroids

KW - Leiomyomas

KW - Treatment

KW - Uterus

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