Biological and Mechanistic Characterization of Novel Prodrugs of Green Tea Polyphenol Epigallocatechin Gallate Analogs in Human Leiomyoma Cell Lines. Issue 10 (28th March 2016)

• Record Type: Journal Article
• Authors: Ahmed, Reda Saber Ibrahim; Liu, Gang; Renzetti, Andrea; Farshi, Pershang; Yang, Huanjie; Soave, Claire; Saed, Ghassan; El‐Ghoneimy, Ashraf Ahmed; El‐Banna, Hossny Awad; Foldes, Robert; Chan, Tak‐Hang; Dou, Q. Ping
• Is Part Of: Journal of cellular biochemistry. Volume 117:Issue 10(2016:Oct.)
• Page Start: 2357
• Page End: 2369
• Publication Date: 2016-03-28
• Subjects: UTERINE FIBROIDS -- LEIOMYOMA -- GREEN TEA -- EGCG ANALOGS -- PRODRUGS -- THERAPY; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25533
• Languages: English
• ISSNs: 0730-2312

Abstract

ABSTRACT: Uterine fibroids (leiomyomas) are very common benign tumors grown on the smooth muscle layer of the uterus, present in up to 75% of reproductive‐age women and causing significant morbidity in a subset of this population. Although the etiology and biology of uterine fibroids are unclear, strong evidence supports that cell proliferation, angiogenesis and fibrosis are involved in their formation and growth. Currently the only cure for uterine fibroids is hysterectomy; the available alternative therapies have limitations. Thus, there is an urgent need for developing a novel strategy for treating this condition. The green tea polyphenol epigallocatechin gallate (EGCG) inhibits the growth of uterine leiomyoma cells in vitro and in vivo, and the use of a green tea extract (containing 45% EGCG) has demonstrated clinical activity without side effects in women with symptomatic uterine fibroids. However, EGCG has a number of shortcomings, including low stability, poor bioavailability, and high metabolic transformations under physiological conditions, presenting challenges for its development as a therapeutic agent. We developed a prodrug of EGCG (Pro‐EGCG or1 ) which shows increased stability, bioavailability and biological activity in vivo as compared to EGCG. We also synthesized prodrugs of EGCG analogs, compounds2a and4a, in order to potentially reduce their susceptibility to methylation/inhibition by catechol‐ O ‐methyltransferase. Here, we determined the effect of EGCG, Pro‐EGCG, and2a and4a on cultured human uterine leiomyoma cells, and found that2a and4a have potent antiproliferative, antiangiogenic, and antifibrotic activities. J. Cell. Biochem. 117: 2357–2369, 2016. © 2016 Wiley Periodicals, Inc. Abstract : This study determined and compared the effect of EGCG, Pro‐EGCG, and2a and4a on cultured human uterine leiomyoma cells, and demonstrated that2a and4a have potent antiproliferative, antiangiogenic, and antifibrotic activities.