Abstract
Uveal melanoma is the most common intraocular malignant tumor in adults. Chrysin is a flavonoid present in honey, propolis, various plants and herbs. In the present study, the cytotoxic effects of chrysin were investigated on human uveal melanoma cell lines (M17 and SP6.5) and associated signaling pathways, and a comparison to the effects on normal ocular cells [scleral fibroblasts and retinal pigment epithelial (RPE) cells] was performed. The effects of chrysin on cell viability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was determined by using terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling assay. Mitochondrial permeability was determined by JC-1 fluorescein analysis. Cytosol cytochrome c levels, and the activities of caspase-3, -8 and -9 were measured by enzyme-linked immunosorbent assay or colorimetric assay. Chrysin reduced the viability of cultured human melanoma cells in a dose-dependent manner (0, 10, 30 and 100 µM) with IC50 at 28.3 and 35.8 µM in SP6.5 and M17 cell lines, respectively. Chrysin at 30-100 µM levels selectively reduced the viability of melanoma cells without affecting the viability of scleral fibroblasts and RPE cells. Chrysin increased mitochondrial permeability, the levels of cytosol cytochrome c, and caspase-9 and -3 activities, but not capase-8 activity in uveal melanoma cells. The results of the present study indicate that chrysin induces apoptosis of human uveal melanoma cells via the mitochondrial signaling pathway and suggest that chrysin may be a promising agent in the treatment of uveal melanoma.