Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth

Small molecules that specifically inhibit the canonical WNT/b-catenin pathway attenuate growth and proliferation of human uterine leiomyoma cell primary cultures.

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Authors

Masanori Ono, M.D., Ph.D., Ping Yin, Ph.D., Antonia Navarro, M.Sc., Molly B. Moravek, M.D., John S. Coon, M.Sc., Stacy A. Druschitz, B.Sc., Cara J. Gottardi, Ph.D., Serdar E. Bulun, M.D.

Volume 101, Issue 5, Pages 1441–1449.e1

Abstract

Objective:

To assess the effect of three WNT/β-catenin pathway inhibitors—inhibitor of β-catenin and TCF4 (ICAT), niclosamide, and XAV939—on the proliferation of primary cultures of human uterine leiomyoma cells.

Design:

Prospective study of human leiomyoma cells obtained from myomectomy or hysterectomy.

Setting:

University research laboratory.

Patient(s):

Women (n = 38) aged 27–53 years undergoing surgery.

Intervention(s):

Adenoviral ICAT overexpression or treatment with varying concentrations of niclosamide or XAV939.

Main Outcome Measure(s):

Cell proliferation, cell death, WNT/-catenin target gene expression or reporter gene regulation, β-catenin levels, and cellular localization.

Result(s):

Inhibitor of β-catenin and TCF4, niclosamide, or XAV939 inhibit WNT/β-catenin pathway activation and exert antiproliferative effects in primary cultures of human leiomyoma cells.

Conclusion(s):

Three WNT/-catenin pathway inhibitors specifically block human leiomyoma growth and proliferation, suggesting that the canonical WNT pathway may be a potential therapeutic target for the treatment of uterine leiomyoma. Our findings provide rationale for further preclinical and clinical evaluation of ICAT, niclosamide, and XAV939 as candidate antitumor agents for uterine leiomyoma.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)00048-X/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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