Abstract
Purpose:
To evaluate the effect of deferoxamine, an iron chelator used in clinical practice, on the growth of uveal melanoma cell lines.
Methods:
Two different uveal melanoma cell lines (MEL 270 and MEL285) were treated with various doses of deferoxamine (0.05 - 0.2 mg/ml). Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Cell cycle analysis was conducted by flow cytometry; additionally, expression of cell-cycle control proteins and cell growth transcription factors, was determined by Western blot.
Results:
Treatment with deferoxamine inhibited cell growth in a dose dependent manner and caused cell cycle arrest in G1 phase after 1 and 2 days of treatment and in S phase after 4 days of treatment. There was a significant increase in the population of apoptotic cells, as determined by flow cytometry. Deferoxamine decreased phosphorylation of ribosomal S6 kinase and decreased expression of cyclin D1 and cyclin dependent kinase 2. Furthermore, it resulted in activation of pro-apoptotic molecule Bcl2 and pro-senescence molecule p21.
Conclusions:
Deferoxamine inhibits proliferation of uveal melanoma cells in vitro via cell cycle arrest and pro-apoptotic mechanisms. These effects were seen at doses encountered in clinical use of Deferoxamine. In vivo animal studies are needed to further examine its potential for treatment of patients suffering from uveal melanoma.