Curcumin Induces Cell Death in Human Uveal Melanoma Cells through Mitochondrial Pathway

Purpose: To study the cytotoxic effects and related signaling pathways of curcumin on human uveal melanoma cells in vitro. Materials and Methods: Two human uveal melanoma cell lines (M21 and SP6.5), scleral fibroblasts, and choroidal melanocytes were treated with curcumin. The effects of curcumin on cell viability were assessed by using the MTT (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide) assay. Cytosol cytochrome c levels and the activities of caspase-9 and caspase-3 were measured by using an enzyme-linked immunosorbent assay. Results: Curcumin induced cell death of cultured human uveal melanoma cells in a dose-dependent manner (10, 30, and 100 mu M) and time-dependent manner (3-48 hr), with IC50 at 19.05 mu M and 22.39 mu M in M21 and SP6.5 cell lines, respectively. Curcumin at lower concentrations (10-30 mu M) selectively reduced the cell viability of uveal melanoma cells, without affecting cell viability of fibroblasts and choroidal melanocytes. Curcumin significantly increased the level of cytosol cytochrome c (2-fold greater than the controls after 2 hr treatment), caspase-9 and caspase-3 activities (approximately 4.5- and 6-fold greater than the controls after 2-6 hr treatment, respectively) in a dose-dependent manner. Conclusions: Curcumin has selectively potent cytotoxic effects on cultured human uveal melanoma cells. This effect is associated with the release of cytochrome c from the mitochondria and the activation of caspase-9 and caspase-3 in uveal melanoma cells after treatment with curcumin.