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.