Leiomyoma fibrosis inhibited by liarozole a retinoic acid metabolic blocking agent

Capsule:
Proliferation of leiomyoma cells was inhibited by treatment with suprapharmacologic concentrations of liarozole, and extracellular matrix mRNA expression decreased in a dose-dependent manner when treated with pharmacologic concentrations of liarozole.

Authors:
Melissa Gilden, B.S., Minnie Malik, Ph.D., Joy Britten, M.D., Tania Delgado, B.S., Gary Levy, M.D., William Catherino, M.D., Ph.D.

Volume 98, Issue 6, Pages 1557-1562, December 2012

Abstract:

Objective:
To study the influence of liarozole on leiomyoma cell proliferation and extracellular matrix (ECM) gene expression in immortalized leiomyoma cells.

Design:
Laboratory study.

Setting:
University hospital.

Patients(s):
None.

Intervention(s):
Tissue culture, real-time reverse transcription-polymerase chain reaction, Western blot.

Main Outcome Measure(s):
Proliferation, mRNA, and ECM protein expression.

Result(s):
Proliferation of leiomyoma cells was inhibited by treatment with liarozole at suprapharmacological concentrations. The mRNA and protein expression of COL1A1, COL4A2, versican, fibromodulin and fibronectin were increased in untreated leiomyoma cells compared with untreated patient-matched myometrial cells. Extracellular matrix mRNA expression was decreased in a dose dependent manner in leiomyoma cells treated with pharmacologic concentrations of liarozole. In addition, myometrial cells treated with liarozole demonstrated no significant alteration in ECM regulation.

Conclusion(s):
Liarozole inhibited ECM protein production at pharmacologic concentrations in immortalized human leiomyoma cells. Retinoic acid metabolic blocking agents represent a potential therapeutic drug family for human leiomyomas.

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