Simvastatin, at clinically relevant concentrations, affects human uterine leiomyoma growth and extracellular matrix production

Simvastatin at pharmacologically relevant concentrations induced apoptosis in human leiomyoma cells and a significant decrease in extracellular matrix proteins, including collagens, fibronectin, and proteoglycans.

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Volume 110, Issue 7, Pages 1398–1407.e1

Authors:

Minnie Malik, Ph.D., Joy Britten, M.D., Mostafa Borahay, M.D., James Segars, M.D., William H. Catherino, M.D., Ph.D.

Abstract:

Objective

To observe the antifibroid effects of therapeutic concentrations of simvastatin, which interferes with cholesterol biosynthesis, a known precursor of five major classes of steroid hormones, including progesterone and estrogen, which play a major role in the development and growth of uterine leiomyomas.

Design

Two-dimensional and three-dimensional cell culture study of immortalized human leiomyoma and patient-matched myometrium cells treated with simvastatin.

Setting

University laboratory.

Patient(s)

None.

Interventions(s)

None.

Main Outcome Measure(s)

Cell proliferation, alteration in apoptotic signaling pathways, and extracellular matrix (ECM) protein production.

Result(s)

Simvastatin demonstrated a concentration-dependent antiproliferative effect on both the leiomyoma cells and the patient-matched myometrium cells, but a higher inhibitory effect at lower concentrations of simvastatin was observed in leiomyoma cells. Simvastatin also regulated leiomyoma cell apoptosis through a concentration-dependent increase in activity of caspase-3. Simvastatin significantly inhibited expression of major ECM proteins collagen I, collagen III, fibronectin, versican, and brevican in leiomyoma cells at concentrations as low as 10−9 mol/L within 48 hours of exposure.

Conclusion(s)

Simvastatin induces apoptosis in uterine leiomyoma cells at low concentrations, as evidenced by increased active caspase levels. Furthermore, inhibited production of the ECM proteins may lead to reduction in tumor size. Simvastatin may represent a novel therapeutic treatment strategy for uterine leiomyomas.


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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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