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Inhibition of leiomyoma cell proliferation in vitro by genistein and the protein tyrosine kinase inhibitor TKS050

Authors :
Shushan, Asher
Ben-Bassat, Hannah
Mishani, Eyal
Laufer, Neri
Klein, Benjamine Y.
Rojansky, Nathan
Source :
Fertility & Sterility. Jan2007, Vol. 87 Issue 1, p127-135. 9p.
Publication Year :
2007

Abstract

Objective: To determine the potency of TKS050, a new epidermal growth factor receptor (EGFR) inhibitor and genistein, a naturally occurring protein tyrosine kinase inhibitor, to inhibit leiomyoma cell proliferation in vitro. Design: Establishment of paired cultures of leiomyoma and normal myometrial samples. Setting: University clinical research laboratory. Patient(s): Hysterectomy specimens from premenopausal women affected by uterine leiomyomas. Intervention(s): The suppressive effect of TKS050 and genistein on the cells, before and after steroidal hormone treatment, was examined. Main Outcome Measure(s): Cell proliferation, recovery after treatment, cell cycle analysis, and immunochemical analysis of relevant proteins were performed. Result(s): TKS050 (2 μmol/L) and genistein (50 μmol/L) completely suppressed leiomyoma cell proliferation, and the cells did not recover after cessation of treatment. TKS050 induced cell cycle arrest and apoptosis in a dose- and time-dependent manner. Cells accumulated in the G0/G1 phase of the cell cycle at the expense of the S and G2+M phases. Treatment of cells with TKS050 resulted in a dose-dependent inhibition of EGFR autophosphorylation and of phosphorylated signal transducer and activator of transcription 3 (Stat3). Genistein inhibited the phosphorylated Stat3 but did not affect EGFR autophosphorylation. The inhibitory effects of TKS050 or genistein were unaffected by the presence of physiologic concentrations of estradiol-17β. Conclusion(s): Leiomyoma cell growth is effectively blocked by TKS050 and genistein. The inhibitory action of newly developed and natural inhibitors derived from diet may be useful as a possible alternative therapy for leiomyomas. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
00150282
Volume :
87
Issue :
1
Database :
Academic Search Index
Journal :
Fertility & Sterility
Publication Type :
Academic Journal
Accession number :
23562968
Full Text :
https://doi.org/10.1016/j.fertnstert.2006.05.056