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  • Title: Inhibition of leiomyoma cell proliferation in vitro by genistein and the protein tyrosine kinase inhibitor TKS050.
    Author: Shushan A, Ben-Bassat H, Mishani E, Laufer N, Klein BY, Rojansky N.
    Journal: Fertil Steril; 2007 Jan; 87(1):127-35. PubMed ID: 17074332.
    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 micromol/L) and genistein (50 micromol/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 G(0)/G(1) phase of the cell cycle at the expense of the S and G(2)+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-17beta. 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.
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