Department of Obstetrics & Gynecology

University of Michigan Health System

Objective: Leiomyomas are one of the commonest benign tumors affecting women, and represent the leading cause of hysterectomy in the United States. The costs and associated morbidity of surgical treatment remain significant. As yet, no effective long-term medical therapy exists in clinical use. However such therapies are being sought.

Study Design: Apoptosis is a process of programmed cell death, and has been widely studied at the cellular and molecular levels. The use of pro-apoptotic agents has been evaluated for a variety of malignant neoplasms.

Method: In our preliminary study, we evaluate the potential of two agents, Bz-423 and resveratrol, for their in vitro pro-apoptotic activity against cultured ELT3 cells, a leiomyoma cell line. Bz-423 is a modified benzodiazepine that acts on the mitochondrion, initiating a chain of events resulting in apoptotic cell death. Resveratrol is a naturally-occurring stilbene compound found in red wine, and has also been shown to induce apoptosis in vitro.

Results: Our results show both compounds are active in promoting cell death in leiomyoma cells. Further studies are planned using flow cytometry to assess the cell-cycle status of the killed and surviving cells, as well as to elucidate the pathways leading to cell death.

If toxicity to other tissues can be minimized, these compounds are potential candidates for development of new therapeutic approaches to uterine leiomyomata, which will be distinct from traditional chemotherapeutic approaches to malignant disease.

Future Plans - In July, Dr. Rehman will move to Dallas, Texas with his wife and daughters. He will start a three-year fellowship program in Reproductive Endocrinology at the University of Texas Southwestern.